Anatomy and physiology of hematopoiesis

Childhood Leukemias, Second Edition

Volumn , Issue , 2006, Pages 69-105

  Eaves, Connie J ^a   Eaves, Allen C ^a  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84932615111     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1017/CBO9780511471001.005     Document Type: Chapter

References (517)

1. Williams, W. J., Beutler, E., Erslev, A. J., &Lichtman, M.A. (eds.). Hematology, 4th edn (New York:McGraw-Hill, 1990).
2. Killmann, S. A., Cronkite, E. P., Fliedner, T. M., & Bond, V. P. Mitotic indices of human bone marrow cells. I. Number and cytologic distribution of mitoses. Blood, 1962; 19: 743-50.
3. Killmann, S. A., Cronkite, E. P., Fliedner, T. M., & Bond, V. P. Mitotic indices of human bone marrow cells. III. Duration of some phases of erythrocytic and granulocytic proliferation computed from mitotic indices. Blood, 1964; 24: 267-80.
4. Warner, H. R., & Athens, J.W. An analysis of granulocyte kinetics in blood and bone marrow. Ann N Y Acad Sci, 1964; 113: 523-36.
5. Dameshek, W. Some speculations on the myeloproliferative syndromes. Blood, 1951; 6: 372-5.
6. Barnes, D. W. H., Ford, C. E., Gray, S. M., & Loutit, J. F. Spontaneous and induced changes in cell populations in heavily irradiated mice. In J. C. Bugher, J. Coursaget, & J. F. Loutit, eds., Progress in Nuclear Energy (Series VI) (London: Pergamon Press, 1959), pp. 1-10.
7. Whang, J., Frei, E., III, Tjio, J. H., Carbone, P. P., & Brecher, G. The distribution of the Philadelphia chromosome in patients with chronic myelogenous leukemia. Blood, 1963; 22: 664-73.
8. Rastrick, J. M., Fitzgerald, P. H., & Gunz, F. W. Direct evidence for presence of Ph1 chromosome in erythroid cells. Br Med J, 1968; 1: 96-8.
9. Turhan, A. G., Humphries, R. K., Phillips, G. L., Eaves, A. C., & Eaves, C. J. Clonal hematopoiesis demonstrated by X-linked DNApolymorphisms after allogeneic bone marrowtransplantation. NEngl J Med, 1989; 320: 1655-61.
10. Eaves, C. J. Myelopoiesis. In E. S. Henderson, T. A. Lister, & M.F. Greaves, eds., Leukemia, 7th edn. (Philadelphia, PA:W. B. Saunders, 2002), pp. 19-45.
11. Palis, J., Robertson, S., Kennedy, M., Wall, C., &Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development, 1999; 126: 5073-84.
12. Moore, M. A. S. & Metcalf, D. Ontogeny of the haemopoietic system; yolk sac origin of in vivo and in vitro colony forming cell in the developing mouse embryo. Br J Haematol, 1970; 18: 279-86.
13. Houssaint, E. Differentiation of the mouse hepatic primordium. II. Extrinsic origin of the haemopoietic cell line. Cell Differ, 1981; 10: 243-52.
14. Wong, P. M. C., Chung, S. W., Chui, D. H. K., & Eaves, C. J. Properties of the earliest clonogenic hemopoietic precursors to appear in the developing murine yolk sac. Proc Natl Acad Sci U S A, 1986; 83: 3851-4.
15. Huang, H., Zettergren, L. D., & Auerbach, R. In vitro differentiation of B cells andmyeloid cells fromthe early mouse embryo and its extraembryonic yolk sac. Exp Hematol, 1994; 22: 19-25.
16. Dzierzak, E. Hematopoietic stem cells and their precursors: developmental diversity and lineage relationships. Immunol Rev, 2002; 187: 126-38.
17. Peault, B. & Tavian, M. Hematopoietic stem cell emergence in the human embryo and fetus. Ann N Y Acad Sci, 2003; 996: 132-40.
18. Johnson, G. R. & Moore, M. A. S. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis. Nature, 1975; 258: 726-8.
19. Delassus, S. & Cumano, A. Circulation of hematopoietic progenitors in the mouse embryo. Immunity, 1996; 4: 97-106.
20. Eaves, C. J. Manipulating hematopoietic stem cell amplification with Wnt. Nat Immunol, 2003; 4: 511-2.
21. Reya, T., Duncan, A. W., Ailles, L., et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature, 2003; 423: 409-14.
22. Rich, I. N. & Kubanek, B. The ontogeny of erythropoiesis in the mouse detected by the erythroid colony-forming technique. J Embryol Exp Morphol, 1980; 58: 143-55.
23. Roodman, G. D. & Zanjani, E. Endogenous erythroid colonyforming cells in fetal and newbornsheep. J Lab Clin Med, 1979; 94: 699-707.
24. Nakano, T., Kodama, H., & Honjo, T. In vitro development of primitive and definitive erythrocytes from different precursors. Science, 1996; 272: 722-4.
25. Migliaccio, A. R. & Migliaccio, G. Human embryonic hemopoiesis: control mechanisms underlying progenitor differentiation in vitro. Dev Biol, 1988; 125: 127-34.
26. Kurata, H., Mancini, G. C., Alespeiti, G., Migliaccio, A. R., & Migliaccio, G. Stem cell factor induces proliferation and differentiation of fetal progenitor cells in the mouse. Br J Haematol, 1998; 101: 676-87.
27. Miller, C. L., Rebel, V. I., Lemieux, M. E., et al. Studies of W mutantmiceprovideevidencefor alternatemechanismscapable of activating hematopoietic stem cells. Exp Hematol, 1996; 24: 185-94.
28. Miller, C. L., Rebel, V. I., Helgason, C. D., Lansdorp, P. M., & Eaves, C. J. Impaired steel factor responsiveness differentially affects the detection and longterm maintenance of fetal liver hematopoietic stem cells in vivo. Blood, 1997; 89: 1214-23.
29. Roy, V., Miller, J. S., & Verfaillie, C. M. Phenotypic and functional characterization of committed and primitive myeloid and lymphoid hematopoietic precursors in human fetal liver. Exp Hematol, 1997; 25: 387-94.
30. Glimm, H. & Eaves, C. J. Direct evidence for multiple selfrenewal divisions of human in vivo repopulating hematopoietic cells in short-termculture. Blood, 1999; 94: 2161-8.
31. Barker, J. E. Development of the mouse hematopoietic system. Dev Biol, 1968; 18: 14-29.
32. Kazazian, H. H., Jr. &Woodhead, A. P. Hemoglobin A synthesis in the developing fetus. NEngl J Med, 1973; 289: 58-62.
33. Weissman, I. L. Developmental switches in the immune system. Cell, 1994; 76: 207-18.
34. Sanchez, M.-J., Holmes, A., Miles, C., & Dzierzak, E. Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo. Immunity, 1996; 5: 513-25.
35. Yoder, M. C., Hiatt, K., Dutt, P., et al. Characterization of definitive lymphohematopoietic stem cells in the day 9 murine yolk sac. Immunity, 1997; 7: 335-44.
36. Huang, H. & Auerbach, R. Identification and characterization of hematopoietic stem cells from the yolk sac of the early mouse embryo. Proc Natl Acad Sci U S A, 1993; 90: 10110-4.
37. Morrison, S. J., Hemmati, H. D., Wandycz, A. M., & Weissman, I. L. The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A, 1995; 92: 10 302-6.
38. Randall, T. D. & Weissman, I. L. Phenotypic and functional changesinducedat the clonal level in hematopoieticstemcells after 5-fluorouracil treatment. Blood, 1997; 89: 3596-606.
39. Rebel, V. I., Miller, C. L., Thornbury, G. R., et al. Acomparison of long-termrepopulating hematopoietic stem cells in fetal liver and adult bone marrow from the mouse. Exp Hematol, 1996; 24: 638-48.
40. Bhatia, M., Bonnet, D., Murdoch, B., Gan, O. I., & Dick, J. E. A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med, 1998; 4: 1038-45.
41. Uchida, N., Dykstra, B., Lyons, K., et al. ABC transporter activities ofmurine hematopoietic stem cells vary according to their developmental and activation status. Blood, 2004; 103: 4487-95.
42. Rebel, V. I., Miller, C. L., Eaves, C. J., & Lansdorp, P. M. The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their adult bone marrowcounterparts. Blood, 1996; 87: 3500-7.
43. Pawliuk, R., Eaves, C., & Humphries, R. K. Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo. Blood, 1996; 88: 2852-8.
44. Nicolini, F. E., Holyoake, T. L., Cashman, J.D., et al.Unique differentiation programs of human fetal liver stem cells revealed both in vitro and in vivo in NOD/SCID mice. Blood, 1999; 94: 2686-95.
45. Cumano, A., Paige, C. J., Iscove, N. N., & Brady, G. Bipotential precursors of B cells and macrophages in murine fetal liver. Nature, 1992; 356: 612-15.
46. Mebius, R. E., Miyamoto, T., Christensen, J., et al. The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3-cells, as well as macrophages. J Immunol, 2001; 166: 6593-601.
47. Sheridan, B. L., Weatherall, D. J., Clegg, J. B., et al. The patterns of fetal haemoglobin production in leukaemia. Br J Haematol, 1976; 32: 487-506.
48. Till, J. E. &McCulloch, E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res, 1961; 14: 213-22.
49. Szilvassy, S. J., Humphries, R. K., Lansdorp, P. M., Eaves, A. C., & Eaves, C. J. Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. Proc Natl Acad Sci U S A, 1990; 87: 8736-40.
50. Conneally, E., Cashman, J., Petzer, A., & Eaves, C. Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity innonobesediabetic-scid/scid mice. Proc Natl Acad Sci U S A, 1997; 94: 9836-41.
51. Fazekas, de St. Groth, S. The evaluation of limiting dilution assays. J Immunol Methods, 1982; 49: R11-23.
52. Fowler, J. H., Wu, A. M., Till, J. E., McCulloch, E. A., & Siminovitch, L. The cellular composition of hemopoietic spleen colonies. J Cell Physiol, 1967; 69: 65-72.
53. Metcalf, D. Hemopoietic Colonies: In Vitro Cloning of Normal and Leukemic Cells (Berlin, Heidelberg: Springer, 1977).
54. Sutherland, H. J., Lansdorp, P. M., Henkelman, D. H., Eaves, A. C., & Eaves, C. J. Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrowstromal layers. Proc Natl Acad SciUSA, 1990; 87: 3584-8.
55. Lemieux, M. E., Rebel, V. I., Lansdorp, P. M., &Eaves, C. J. Characterization and purification of a primitive hematopoietic cell typeinadultmousemarrowcapableoflympho-myeloid differentiation in long-termmarrow "switch" cultures. Blood, 1995; 86: 1339-47.
56. Trevisan, M. & Iscove, N. Phenotypic analysis of murine longterm hematopoietic reconstituting cells quantitated competitively in vivo and comparison with more advanced colonyforming progeny. J Exp Med, 1995; 181: 93-103.
57. Audet, J., Miller, C. L., Rose-John, S., Piret, J., & Eaves, C. J. Distinct role of gp130 activation in promoting self-renewal divisions by mitogenically stimulatedmurine hematopoietic stem cells. Proc Natl Acad Sci U S A, 2001; 98: 1757-62.
58. Osawa, M., Hanada, K. I., Hamada, H., & Nakauchi, H. Longterm lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science, 1996; 273: 242-5.
59. McCulloch, E. A. Stem cells in normal and leukemic hemopoiesis. Blood, 1983; 62: 1-13.
60. Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997; 3: 730-6.
61. Raskind, W. H. & Fialkow, P. J. The use of cell markers in the study of human hematopoietic neoplasia. Adv Cancer Res, 1987; 49: 127-67.
62. Fearon, E. R., Burke, P. J., Schiffer, C. A., Zehnbauer, B. A., & Vogelstein, B. Differentiation of leukemia cells to polymorphonuclear leukocytes in patients with acute nonlymphocytic leukemia. NEngl J Med, 1986; 315: 15-24.
63. McCulloch, E. A., Siminovitch, L., & Till, J. E. Spleen colony formation in anemic mice of genotype W/Wv. Science, 1964; 144: 844-6.
64. Juraskova, V. & Tkadlecek, L. Character of primary and secondary colonies of haematopoieses in the spleen of irradiated mice. Nature, 1965; 206: 951-2.
65. Boggs, S. S., Chervenick, P. A., & Boggs, D. R. The effect of postirradiation bleeding or endotoxin on proliferation and differentiation of hematopoietic stem cells. Blood, 1972; 40: 375-89.
66. Gregory, C. J., McCulloch, E. A., & Till, J. E. Transient erythropoietic spleen colonies: effects of erythropoietin innormaland genetically anemic W/Wv mice. J Cell Physiol, 1975; 86: 1-8.
67. Siminovitch, L., McCulloch, E. A., & Till, J. E. The distribution of colony-forming cells among spleen colonies. J Cell Physiol, 1963; 62: 327-36.
68. Magli, M. C., Iscove, N. N., &Odartchenko, N. Transient nature of early haematopoietic spleen colonies. Nature, 1982; 295: 527-9.
69. Gregory, C. J. &Henkelman, R. M. Relationships between early hemopoietic progenitor cells determined by correlation analysis of their numbers in individual spleen colonies. In S. J. Baum & G. D. Ledney, eds., Experimental Hematology Today (New York: Springer, 1977), pp. 93-101.
70. Hodgson, G. S. & Bradley, T. R. Properties of hematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell? Nature, 1979; 281: 381-2.
71. Worton, R. G., McCulloch, E. A., & Till, J. E. Physical separation of hemopoietic stem cells differing in their capacity for selfrenewal. J Exp Med, 1969; 130: 91.
72. Bertoncello, I., Hodgson, G. S., & Bradley, T. R. Multiparameter analysis of transplantable hemopoietic stem cells. II. Stem cells of long-termbone marrow-reconstituted recipients. Exp Hematol, 1988; 16: 245-9.
73. Spangrude, G. J. & Johnson, G. R. Resting and activated subsets of mouse multipotent hematopoietic stem cells. Proc Natl Acad Sci U S A, 1990; 87: 7433-7.
74. Morrison, S. J. & Weissman, I. L. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity, 1994; 1: 661-73.
75. Hodgson, G. S. & Bradley, T. R. In vivo kinetic states of hematopoietic stem and progenitor cells as inferred from labelling with bromodeoxyuridine. Exp Hematol, 1984; 12: 683-7.
76. Dumenil, D., Jacquemin-Sablon, H., Neel, H., Frindel, E., & Dautry, F. Mock retroviral infection alters the developmental potential of murine bone marrow stem cells. Mol Cell Biol, 1989; 9: 4541-4.
77. Wolf, N. S., Kone, A., Priestley, G. V., & Bartelmez, S. H. In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine123 FACS selection. Exp Hematol, 1993; 21: 614-22.
78. Ploemacher, R. E. & Brons, R. H. C. Separation of CFU-S from primitive cells responsible for reconstitution of the bone marrow hemopoietic stem cell compartment following irradiation: evidence for a pre-CFU-S cell. Exp Hematol, 1989; 17: 263-6.
79. Jones, R. J., Collector, M. I., Barber, J. P., et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood, 1996; 88: 487-91.
80. Metcalf, D. &Moore, M. A. S. Haematopoietic cells. In A. Neuberger & E. L. Tatum, eds., Frontiers of Biology (Amsterdam: North-Holland Publishing, 1971), p. 550.
81. Lahiri, S. K., Keizer, H. J., & Putten, L. M. Van. The efficiency of the assay for haemopoietic colony forming cells. Cell Tissue Kinet, 1970; 3: 355-62.
82. Testa, N. G., Lord, B. I., & Shore, N. A. The in vivo seeding of hemopoietic colony-forming cells in irradiated mice. Blood, 1972; 40: 654-61.
83. Lord, B. I. In vivo assays of multipotential and marrowrepopulating cells. In N. G. Testa & G. Molineux, eds., Haemopoiesis: A Practical Approach (New York: Oxford University Press, 1993), pp. 1-20.
84. Wu, A.M., Till, J. E., Siminovitch, L., &McCulloch, E. A. Cytological evidence for a relationship between normal hematopoietic colony-forming cells and cells of the lymphoid system. J Exp Med, 1968; 127: 455-64.
85. Dick, J. E., Magli, M. C., Huszar, D., Phillips, R. A., & Bernstein, A. Introduction of a selectable gene into primitive stem cells capableof long-termreconstitution of thehemopoieticsystem of W/Wv mice. Cell, 1985; 42: 71-9.
86. Keller, G., Paige, C., Gilboa, E., & Wagner, E. F. Expression of a foreign gene in myeloid and lymphoid cells derived from multipotent haematopoietic precursors. Nature, 1985; 318: 149-54.
87. Lemischka, I. R., Raulet, D. H., &Mulligan, R. C. Developmental potential and dynamic behavior of hematopoietic stem cells. Cell, 1986; 45: 917-27.
88. Harrison, D. E. Normal production of erythrocytes by mouse marrow continuous for 73 months. Proc Natl Acad Sci U S A, 1973; 70: 3184-8.
89. Szilvassy, S. J., Nicolini, F. E., Eaves, C. J., & Miller, C. L. Quantitation of murine and human hematopoietic stem cells by limiting-dilution analysis in competitively repopulated hosts. In C. T. Jordon & C. A. Klug, eds. Methods in Molecular Medicine: Hematopoietic Stem Cell Protocols (Totowa, NJ: Humana Press, 2002), pp. 167-87.
90. Jordan, C. T. & Lemischka, I. R. Clonal and systemic analysis of long-termhematopoiesis in the mouse. Genes Dev, 1990; 4: 220-32.
91. Zhong, R.-K., Astle, C. M., & Harrison, D. E. Distinct developmental patterns of short-termand long-termfunctioning lymphoid andmyeloid precursors defined by competitive limiting dilution analysis in vivo. J Immunol, 1996; 157: 138-45.
92. Uchida, N., Dykstra, B., Lyons, K. J., Leung, F. Y. K., &Eaves, C. J. Different in vivorepopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics. Exp Hematol, 2003; 31: 1338-47.
93. Audet, J., Miller, C. L., Eaves, C. J., & Piret, J. M. Common and distinct features of cytokine effectsonhematopoieticstemand progenitor cells revealed by dose response surface analysis. Biotechnol Bioeng, 2002; 80: 393-404.
94. Harrison, D. E. Competitive repopulation: a new assay for long-term stem cell functional capacity. Blood, 1980; 55: 77-81.
95. Harrison, D. E. Evaluating functional abilities of primitive hematopoietic stem cell populations. Curr Top Microbiol Immunol, 1992; 177: 13-30.
96. Benveniste, P., Cantin, C., Hyam, D., &Iscove, N.N. Hematopoietic stem cells engraft in mice with absolute efficiency. Nat Immunol, 2003; 4: 708-13.
97. Matsuzaki, Y., Kinjo, K., Mulligan, R. C., &Okano, H. Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity, 2004; 20: 87-93.
98. Szilvassy, S. J., Ragland, P. L., Miller, C. L., & Eaves, C. J. The marrowhoming efficiency ofmurine hematopoietic stem cells remains constant during ontogeny. Exp Hematol, 2003; 31: 331-8.
99. Kawada, H.&Ogawa, M. Bone marroworigin of hematopoietic progenitors and stem cells in murine muscle. Blood, 2001; 98: 2008-13.
100. McKinney-Freeman, S. L., Jackson, K. A., Camargo, F. D., et al. Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci U S A, 2002; 99: 1341-6.
101. Uchida, N., Leung, F. Y. K., & Eaves, C. J. Liver and marrow of adult mdr-1a/1b-/-mice show normal generation, function and multi-tissue trafficking of primitive hematopoietic cells. Exp Hematol, 2002; 30: 862-9.
102. Ramshaw, H. S., Rao, S. S., Crittenden, R. B., et al. Engraftment of bone marrow cells into normal unprepared hosts: effects of 5-fluorouracil and cell cycle status. Blood, 1995; 86: 924-9.
103. Habibian, H. K., Peters, S.O., Hsieh, C. C., et al. The fluctuating phenotype of the lympho-hematopoietic stem cell with cell cycle transit. J Exp Med, 1998; 188: 393-8.
104. Becker, A. J., McCulloch, E. A., Siminovitch, L., & Till, J. E. The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice. Blood, 1965; 26: 296-308.
105. Toksoz, D., Dexter, T. M., Lord, B. I., Wright, E. G., &Lajtha, L. G. The regulation of hemopoiesis in long-termbone marrowcultures. II. Stimulation and inhibition of stem cell proliferation. Blood, 1980; 55: 931-6.
106. Wang, J. C. Y., Dorrell, C., Ito, C. Y., et al. Normal and leukemic human stem cells assayed in immune-deficient mice. In L. I. Zon, ed., Hematopoiesis: ADevelopmental Approach (New York: Oxford University Press, 2001), pp. 99-118.
107. Kollet, O., Peled, A., Byk, T., et al. _2 microglobulin-deficient (_2mnull)NOD/SCIDmiceare excellent recipients for studying human stem cell function. Blood, 2000; 95: 3102-5.
108. Glimm, H., Eisterer, W., Lee, K., et al. Previously undetected human hematopoietic cell populations with shortterm repopulating activity selectively engraft NOD/SCIDb2 microglobulin-null mice. J Clin Invest, 2001; 107: 199-206.
109. Hiramatsu, H., Nishikomori, R., Heike, T., et al. Complete reconstitution ofhumanlymphocytes fromcordblood CD34+ cells using the NOD/SCID/gammac null mice model. Blood, 2003; 102: 873-80.
110. Goldman, J. P., Blundell, M. P., Lopes, L., et al. Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chain. Br J Haematol, 1998; 103: 335-42.
111. Traggiai, E., Chicha, L., Mazzucchelli, L., et al. Development of a human adaptive immune system in cord blood celltransplanted mice. Science, 2004; 304: 104-7.
112. Zanjani, E. D., Almeida-Porada, G., & Flake, A. W. The human/sheep xenograft model: a large animal model of human hematopoiesis. Int J Hematol, 1996; 63: 179-92.
113. Bernstein, J., Boyle, D. W., Srour, E. F., et al. Variation in longtermengraftment of a large consecutive series of lambs transplanted in utero with human hematopoietic cells. Biol Blood Marrow Transplant, 1997; 3: 247-54.
114. Christianson, S. W., Greiner, D. L., Hesselton, R., et al. Enhanced human CD4+ T cell engraftment in b2-microglobulin-deficient NOD-scid mice. J Immunol, 1997; 158: 3578-86.
115. Cashman, J. D. & Eaves, C. J. High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID mice. Blood, 2000; 96: 3979-81.
116. Ballen, K. K., Valinski, K., Greiner, D., et al. Variables to predict engraftment of umbilical cord blood into immunodeficient mice: usefulness of the non-obese diabetic-severe combined immunodeficient assay. Br J Haematol, 2001; 114: 211-18.
117. Meyerrose, T., Herrbrich, P. E., Hess, D. A., & Nolta, J. A. Immune-deficient mouse models for analysis of human stem cells. Biotechniques, 2003; 35: 1262-71.
118. Srour, E. F., Zanjani, E. D., Cornetta, K., et al. Persistence of human multilineage, self-renewing lymphohematopoietic stem cells in chimeric sheep. Blood, 1993; 82: 3333-42.
119. Civin, C. I., Almeida-Porada, G., Lee, M.-J., et al. Sustained, retransplantable, multilineage engraftment of highly purified adult human bone marrow stem cells in vivo. Blood, 1996; 88: 4102-9.
120. Zanjani, E. D., Almeida-Porada, G., Livingston, A. G., Flake, A. W., &Ogawa, M. Human bone marrow CD34-cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol, 1998; 26: 353-60.
121. Cashman, J. D. & Eaves, C. J. Human growth factor-enhanced regeneration of transplantable human hematopoietic stem cells innonobesediabetic/severecombinedimmunodeficient mice. Blood, 1999; 93: 481-7.
122. Hogan, C. J., Shpall, E. J., McNulty, O., et al. Engraftment and development of human CD34+-enriched cells from umbilical cordblood in NOD/Lt Sz-scid/scid mice. Blood, 1997; 90: 85-96.
123. Hogan, C. J., Shpall, E. J., & Keller, G. Differential long-term and multilineage engraftment potential from subfractions of human CD34+ cord blood cells transplanted into NOD/SCID mice. Proc Natl Acad Sci U S A, 2002; 99: 413-18.
124. Pflumio, F., Izac, B., Katz, A., et al. Phenotype and function of human hematopoietic cells engrafting immunedeficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells. Blood, 1996; 88: 3731-40.
125. Cashman, J., Bockhold, K., Hogge, D. E., Eaves, A. C., & Eaves, C. J. Sustained proliferation, multi-lineage differentiation and maintenance of primitive human haematopoietic cells in NOD/SCID mice transplanted with human cord blood. Br J Haematol, 1997; 97: 1026-36.
126. Lapidot, T., Pflumio, F., Doedens, M., et al. Cytokine stimulation of multilineage hematopoiesis from immature human cells engrafted in SCID mice. Science, 1992; 255: 1137-41.
127. Cashman, J. D., Lapidot, T., Wang, J. C. Y., et al. Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive cells in normal human bone marrow transplanted into immunodeficient mice. Blood, 1997; 89: 4307-16.
128. Peled, A., Petit, I., Kollet, O., et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science, 1999; 283: 845-8.
129. Holyoake, T. L., Nicolini, F. E., & Eaves, C. J. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol, 1999; 27: 1418-27.
130. Rossi, M. I. D., Medina, K. L., Garrett, K., et al. Relatively normal human lymphopoiesis but rapid turnover of newly formed B cells in transplanted nonobese diabetic/SCID mice. J Immunol, 2001; 167: 3033-42.
131. Nicolini, F. E., Cashman, J.D., Hogge, D. E., Humphries, R. K., & Eaves, C. J. NOD/SCID mice engineered to express human IL-3, GM-CSF, and Steel factor constitutively mobilize engrafted human progenitors and compromise human stem cell regeneration. Leukemia, 2004; 18: 341-7.
132. Kerre, T. C., De Smet, G., De Smedt, M., et al. Both CD34+38+ and CD34+38-cells home specifically to the bone marrow of NOD/LtSZscid/scidmicebutshowdifferent kinetics inexpansion. J Immunol, 2001; 167: 3692-8.
133. Mazurier, F., Doedens, M., Gan, O. I., &Dick, J. E. Rapidmyeloerythroid repopulation after intrafemoral transplantation of NOD-SCID mice reveals a new class of human stem cells. Nat Med, 2003; 9: 959-63.
134. Glimm, H., Oh, I., &Eaves, C. Humanhematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/Mtransitanddonot reenter Go. Blood, 2000; 96: 4185-93.
135. Wang, J. C. Y., Doedens, M., & Dick, J. E. Primitive human hematopoietic cells are enriched in cord blood compared with adultbonemarrowor mobilizedperipheral blood asmeasured bythe quantitativein vivo SCID-repopulating cell assay. Blood, 1997; 89: 3919-24.
136. Ailles, L. E., Gerhard, B., Kawagoe, H., & Hogge, D. E. Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese Cambridge Books Online (c) Cambridge University Press, 2009 Anatomy and physiology of hematopoiesis 93 diabetic/severe combined immunodeficient mice. Blood, 1999; 94: 1761-72.
137. Rombouts, W. J. C., Martens, A. C. M., & Ploemacher, R. E. Identificationofvariablesdeterminingtheengraftmentpotential ofhumanacutemyeloid leukemia in the immunodeficient NOD/SCID human chimera model. Leukemia, 2000; 14: 889-97.
138. Feuring-Buske, M., Gerhard, B., Cashman, J., et al. Improved engraftment of human acute myeloid leukemia progenitor cells in beta 2-microglobulin-deficient NOD/SCID mice and in NOD/SCID mice transgenic for human growth factors. Leukemia, 2003; 17: 760-3.
139. Kamel-Reid, S., Letarte, M., Sirard, C., et al. A model of human acute lymphoblastic leukemia in immune-deficient SCID mice. Science, 1989; 246: 1597-600.
140. Nijmeijer, B. A., Mollevanger, P., van Zelderen-Bhola, S. L., et al. Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice. Exp Hematol, 2001; 29: 322-9.
141. Eisterer, W., Jiang, X., Bachelot, T., et al. Unfulfilled promise of endostatin in a gene therapy-xenotransplant model of human acute lymphocytic leukemia. Mol Ther, 2002; 5: 352-9.
142. Sawyers, C. L., Gishizky, M. L., Quan, S., Golde, D.W., &Witte, O. N. Propagation of human blastic myeloid leukemias in the SCID mouse. Blood, 1992; 79: 2089-98.
143. Sirard, C., Lapidot, T., Vormoor, J., et al. Normal and leukemic SCID-repopulatingcells(SRC)co-exist inthebonemarrowand peripheral blood from CML patients in chronic phase while leukemic SRCaredetected in blast crisis. Blood, 1996;87:1539-48.
144. Pilarski, L. M., Hipperson, G., Seeberger, K., et al. Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and self-renewal of primary human myeloma in the bone marrowof NODSCID mice. Blood, 2000; 95: 1056-65.
145. Matsui, W., Huff, C. A., Wang, Q., et al. Characterization of clonogenic multiple myeloma cells. Blood, 2004; 103: 2332-6.
146. Mitsiades, C. S., Mitsiades, N. S., Bronson, R. T., et al. Fluorescenceimagingof multiplemyelomacells inaclinically relevant SCID/NOD in vivo model: biologic and clinical implications. Cancer Res, 2003; 63: 6689-96.
147. Shimoni, A., Marcus, H., Dekel, B., et al. Autologous T cells control B-chronic lymphocytic leukemia tumor progression in human-mouse radiation chimera. Cancer Res, 1999; 59: 5968-74.
148. Dialynas, D. P., Lee, M-J., Gold, D. P., et al. Preconditioning with fetal cord blood facilitates engraftment of primary childhood T-cell acute lymphoblastic leukemia in immunodeficient mice. Neoplasia, 2001; 97: 3218-25.
149. Terpstra, W., Ploemacher, R. E., Prins, A., et al. Fluorouracil selectively spares acute myeloid leukemia cells with longtermgrowth abilities in immunodeficient mice and in culture. Blood, 1996; 88: 1944-50.
150. Guan, Y., Gerhard, B., & Hogge, D. E. Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells frompatientswithacutemyeloidleukemia(AML). Blood, 2003; 101: 3142-9.
151. Blair, A., Hogge, D. E., Ailles, L. E., Lansdorp, P.M., &Sutherland, H. J. Lack of expression of Thy-1 (CD90) on acute myeloid leukaemia cells with long-termproliferative ability in vitro and in vivo. Blood, 1997; 89: 3104-12.
152. Lapidot, T., Grunberger, T., Vormoor, J., et al. Identification of human juvenile chronic myelogenous leukemia stem cells capable of initiating the disease in primary and secondary SCID mice. Blood, 1996; 88: 2655-64.
153. Thanopoulou, E., Cashman, J., Kakagianne, T., et al. Engraftment of NOD/SCID-b2 microglobulin null mice with multilineage neoplastic cells from patients with myelodysplastic syndrome. Blood, 2004; 103: 4285-93.
154. Lewis, I. D., McDiarmid, L. A., Samels, L. M., Bik To, L., & Hughes, T. P. Establishment of a reproducible model of chronic-phase chronic myeloid leukemia in NOD/SCID mice using blood-derivedmononuclearor CD34+ cells. Blood, 1998; 91: 630-40.
155. Wang, J. C. Y., Lapidot, T., Cashman, J. D., et al. High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase. Blood, 1998; 91: 2406-14.
156. Sutherland, H. J., Eaves, C. J., Eaves, A. C., Dragowska, W., & Lansdorp, P. M. Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. Blood, 1989; 74: 1563-70.
157. Ploemacher, R. E., Sluijs, J. P. Van Der, Beurden, C. A. J. van, Baert, M. R. M., & Chan, P. L. Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrowrepopulating and spleen colony-forming hematopoietic stem cells in the mouse. Blood, 1991; 78: 2527-33.
158. Dexter, T. M., Allen, T. D., & Lajtha, L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol, 1977; 91: 335-44.
159. Greenberger, J. S. Sensitivity of corticosteroid-dependent insulin-resistant lipogenesis in marrow preadipocytes of obese-diabetic (db/db) mice. Nature, 1978; 275: 752-4.
160. Gartner, S. & Kaplan, H. S. Long-term culture of human bone marrow cells. Proc Natl Acad Sci U S A, 1980; 77: 4756-9.
161. Greenberg, H. M., Newburger, P. E., Parker, L. M., Novak, T., & Greenberger, J. S. Human granulocytes generated in continuous bone marrow culture are physiologically normal. Blood, 1981; 58: 724-32.
162. Gronthos, S. & Simmons, P. J. The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood, 1995; 85: 929-40.
163. Roecklein, B. A. & Torok-Storb, B. Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. Blood, 1995; 85: 997-1005.
164. Li, J., Sensebe, L., Herve, P., & Charbord, P. Nontransformed colony-derived stromal cell lines from normal human marrows. III. The maintenance of hematopoiesis from CD34+ cell populations. Exp Hematol, 1997; 25: 582-91.
165. Sutherland, H. J., Eaves, C. J., Lansdorp, P. M., Thacker, J. D., & Hogge, D. E. Differential regulation of primitive human hematopoietic cells in long-term cultures maintained on genetically engineered murine stromal cells. Blood, 1991; 78: 666-72.
166. Issaad, C., Croisille, L., Katz, A., Vainchenker, W., &Coulombel, L. A murine stromal cell line allows the proliferation of very primitive human CD34++/CD38-progenitor cells in longterm cultures and semisolid assays. Blood, 1993; 81: 2916-24.
167. Baum, C. M., Weissman, I. L., Tsukamoto, A. S., Buckle, A. M., & Péault, B. Isolation of a candidatehumanhematopoietic stemcell population. Proc Natl Acad Sci U S A, 1992; 89: 2804-8.
168. Thiemann, F. T., Moore, K. A., Smogorzewska, E. M., Lemischka, I. R., &Crooks, G.M. Themurine stromal cell line AFT024 acts specifically onhumanCD34+CD38-progenitors to maintain primitive function and immunophenotype in vitro. Exp Hematol, 1998; 26: 612-19.
169. Wineman, J., Moore, K., Lemischka, I., & Muller-Sieburg, C. Functional heterogeneity of the hematopoietic microenvironment: rare stromal elements maintain long-term repopulating stem cells. Blood, 1996; 87: 4082-90.
170. Friedrich, C., Zausch, E., Sugrue, S. P., &Gutierrez-Ramos, J.-C. Hematopoietic supportive functions of mouse bone marrow and fetal liver microenvironment: dissection of granulocyte, B-lymphocyte, and hematopoietic progenitor support at the stroma cell clone level. Blood, 1996; 87: 4596-606.
171. Charbord, P., Oostendorp, R., Pang, W., et al. Comparativestudy of stromal cell lines derived from embryonic fetal, and postnatal mouse blood-forming tissues. Exp Hematol, 2004; 30: 1202-10.
172. Moore, K. A., Pytowski, B., Witte, L., Hicklin, D., & Lemischka, I. R. Hematopoietic activity of a stromal cell transmembrane protein containing epidermalgrowthfactor-like repeat motifs. Proc Natl Acad Sci U S A, 1997; 94: 4011-16.
173. Varnum-Finney, B., Purton, L. E., Yu, M., et al. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood, 1998; 91: 4084-91.
174. Karanu, F. N., Murdoch, B., Gallacher, L., et al. The Notch ligand Jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med, 2000; 192: 1365-72.
175. Ohishi, K., Varnum-Finney, B., & Bernstein, I. D. Delta-1 enhances marrow and thymus repopulating ability of human CD34+CD38-cord blood cells. J Clin Invest, 2002; 110: 1165-74.
176. Gupta, P., McCarthy, J. B., & Verfaillie, C. M. Stromal fibroblast heparan sulfate is required for cytokine-mediated ex vivo maintenance ofhumanlong-termculture-initiating cells. Blood, 1996; 87: 3229-36.
177. Gupta, P., Oegema, T. R. J., Brazil, J. J., et al. Structurally specific heparan sulfates support primitive human hematopoiesis by formation of a multimolecular stem cell niche. Blood, 1998; 92: 4641-51.
178. Hogge, D. E., Lansdorp, P. M., Reid, D., Gerhard, B., & Eaves, C. J. Enhanced detection, maintenance and differentiation of primitive human hematopoietic cells in cultures containing murine fibroblasts engineered to produce human Steel factor, interleukin-3 and granulocyte colony-stimulating factor. Blood, 1996; 88: 3765-73.
179. Miller, C. L. & Eaves, C. J. Long-term culture-initiating cell assays for human and murine cells. In C. A. Klug & C. T. Jordan, eds., Methods in Molecular Medicine: Hematopoietic Stem Cell Protocols (Totowa, NJ: Humana Press, 2002), pp. 123-41.
180. Hao, Q. L., Thiemann, F. T., Petersen, D., Smogorzewska, E. M., & Crooks, G. M. Extended long-term culture reveals a highly quiescent and primitivehumanhematopoietic progenitor population. Blood, 1996; 88: 3306-13.
181. Freedman, A. R., Zhu, H., Levine, J. D., Kalams, S., & Scadden, D. T. Generation of human T lymphocytes from bone marrow CD34+ cells in vitro. Nat Med, 1996; 2: 46-51.
182. Punzel, M., Wissink, S. D., Miller, J. S., et al. The myeloidlymphoid initiating cell (ML-IC) assay assesses the fate of multipotent human progenitors in vitro. Blood, 1999; 93: 3750-6.
183. Berardi, A. C., Meffre, E., Pflumio, F., et al. Individual CD34+CD38lowCD19-CD10-progenitor cells from human cord blood generate B lymphocytes and granulocytes. Blood, 1997; 89: 3554-64.
184. Gan, O. I., Dorrell, C., Pereira, D. S., et al. Characterization and retroviral transduction of an earlyhumanlymphomyeloid precursor assayed in nonswitched long-term culture on murine stroma. Exp Hematol, 1999; 27: 1097-106.
185. Harrison, D. E., Lerner, C. P., & Spooncer, E. Erythropoietic repopulating ability of stem cells from long-termmarrow culture. Blood, 1987; 69: 1021-5.
186. Fraser, C. C., Szilvassy, S. J., Eaves, C. J., & Humphries, R. K. Proliferation of totipotent hematopoietic stem cells in vitro with retention of long-termcompetitive in vivo reconstituting ability. Proc Natl Acad Sci U S A, 1992; 89: 1968-72.
187. Moore, K. A., Ema, H., & Lemischka, I. R. In vitro maintenance of highly purified, transplantable hematopoietic stem cells. Blood, 1997; 89: 4337-47.
188. Lemieux, M. E. & Eaves, C. J. Identification of properties that can distinguish primitive populations of stromal cellresponsive lympho-myeloid cells from cells that are stromal cell-responsive but lymphoid-restricted and cells that have lympho-myeloid potential but are also capable of competitively repopulating myeloablated recipients. Blood, 1996; 88: 1639-48.
189. Larochelle, A., Vormoor, J., Hanenberg, H., et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med, 1996; 2: 1329-37.
190. Hennemann, B., Oh, I.-H., Chuo, J. Y., et al. Efficient retrovirusmediatedgenetransfer to transplantablehumanbonemarrow cells in the absence of fibronectin. Blood, 2000; 96: 2432-9.
191. Uchida, N., Fujisaki, T., Eaves, A. C., & Eaves, C. J. Transplantable hematopoietic stem cells in human fetal liver have Cambridge Books Online (c) Cambridge University Press, 2009 Anatomy and physiology of hematopoiesis 95 a CD34+ side population (SP) phenotype. J Clin Invest, 2001; 108: 1071-7.
192. Eaves, C. J. & Eaves, A. C. Progenitor cell dynamics. In A. M. Carella, G.Q. Daley, C.J. Eaves, J.M. Goldman, & R. Hehlmann, eds., Chronic Myeloid Leukemia: Biology and Treatment (London:Martin Dunitz, 2001), pp. 73-100.
193. Coulombel, L., Eaves, C., Kalousek, D., Gupta, C., & Eaves, A. Long-term marrow culture of cells from patients with acute myelogenous leukemia. Selection in favor of normal phenotypes in some but not all cases. J Clin Invest, 1985; 75: 961-9.
194. Sutherland, H. J., Blair, A., & Zapf, R. W. Characterization of a hierarchy in human acute myeloid leukemia progenitor cells. Blood, 1996; 87: 4754-61.
195. Petzer, A. L., Eaves, C. J., Lansdorp, P. M., et al. Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronicmyeloid leukemia. Blood, 1996; 88: 2162-71.
196. Ailles, L. E., Gerhard, B., & Hogge, D. E. Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood, 1997; 90: 2555-64.
197. Young, D. C., Demetri, G. D., Ernst, T. J., Cannistra, S. A., & Griffin, J. D. In vitro expression of colony-stimulating factor genesbyhumanacutemyeloblastic leukemia cells. Exp Hematol, 1988; 16: 378-82.
198. Jiang, X., Lopez, A., Holyoake, T., Eaves, A., & Eaves, C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia. Proc Natl Acad Sci U S A, 1999; 96: 12804-9.
199. Coulombel, L., Kalousek, D. K., Eaves, C. J., Gupta, C. M., & Eaves, A. C. Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. NEngl J Med, 1983; 308: 1493-8.
200. Guan, Y., Ralph, S., Ling, V., & Hogge, D. E. Polyclonal normal hematopoietic progenitors in patients with acutemyeloid leukemia (AML). Exp Hematol, 2002; 30: 721-8.
201. Nara, N. & McCulloch, E. A. The proliferation in suspension of the progenitors of the blast cells in acute myeloblastic leukemia. Blood, 1985; 65: 1484-93.
202. Trevisan, M., Yan, X.-Q., & Iscove, N. N. Cycle initiation and colony formation in culture by murine marrow cells with long-term reconstituting potential in vivo. Blood, 1996; 88: 4149-58.
203. Petzer, A. L., Hogge, D. E., Lansdorp, P. M., Reid, D. S., & Eaves, C. J. Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium. Proc Natl Acad Sci U S A, 1996; 93: 1470-4.
204. Maguer-Satta, V., Oostendorp, R., Reid, D., & Eaves, C. J. Evidence that ceramide mediates the ability of tumor necrosis factor to modulate primitive human hematopoietic cell fates. Blood, 2000; 96: 4118-23.
205. Bradley, T. R., &Metcalf, D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci, 1966; 44: 287-300.
206. Pluznik, D. H., & Sachs, L. The cloning of normal "mast" cells in tissue culture. J Cell Comp Physiol, 1965; 66: 319-24.
207. Senn, J. S., McCulloch, E. A., & Till, J. E. Comparison of colonyforming ability of normal and leukaemic human marrow in cell culture. Lancet, 1967; 2: 597-8.
208. Worton, R. G., McCulloch, E. A., & Till, J. E. Physical separation of hemopoietic stem cells from cells forming colonies in culture. J Cell Physiol, 1969; 74: 171-82.
209. Metcalf, D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science, 1991; 254: 529-33.
210. Metcalf, D. The granulocyte-macrophage regulators: reappraisal by gene inactivation. Exp Hematol, 1995; 23: 569-72.
211. Campbell, H. D., Tucker, W. Q. J., Hort, Y., et al. Molecular cloning, nucleotide sequence, and expression of the gene encodinghumaneosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci U S A, 1987; 84: 6629-33.
212. Yamaguchi, Y., Suda, T., Suda, J., et al. Purified 5. interleukin upports the terminal differentiation and proliferation of murine eosinophilic precursors. J Exp Med, 1988; 167: 43-56.
213. Lord, B. I., Gurney, H., Chang, J., et al. Haemopoietic cell kinetics in humans treated with rGM-CSF. Int J Cancer, 1992; 50: 26-31.
214. Williams, G. T., Smith, C. A., Spooncer, E., Dexter, T. M., & Taylor, D. R. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature, 1990; 343: 76-9.
215. Bol, S. & Williams, N. The maturation state of three types of granulocyte/macrophage progenitor cells from mouse bone marrow. J Cell Physiol, 1980; 102: 233-43.
216. Metcalf, D. & Mac Donald, H. R. Heterogeneity of in vitro colony-and cluster-forming cells in the mouse marrow: segregation by velocity sedimentation. J Cell Physiol, 1975; 85: 643-54.
217. Cashman, J., Eaves, A. C., & Eaves, C. J. Regulated proliferation of primitive hematopoietic progenitor cells in long-term human marrow cultures. Blood, 1985; 66: 1002-5.
218. Gregory, C. J. Erythropoietin sensitivity as a differentiation marker in the hemopoietic system: studies of three erythropoietic colony responses in culture. J Cell Physiol, 1976; 89: 289-301.
219. Stephenson, J. R., Axelrad, A. A., McLeod, D. L., & Shreeve, M. M. Induction of colonies of hemoglobin-synthesising cells by erythropoietin in vitro. Proc Natl Acad Sci U S A, 1971; 68: 1542-6.
220. Heath, D. S., Axelrad, A. A., McLeod, D. L., & Shreeve, M. M. Separation of the erythropoietin-responsive progenitors BFUE and CFU-E in mouse bone marrow by unit gravity sedimentation. Blood, 1976; 47: 777-92.
221. Clark, B. J. & Housman, D. Characterization of an erythroid precursor cell of high proliferative capacity in normal human peripheral blood. Proc Natl Acad Sci U S A, 1977; 74: 1105-9.
222. Eaves, C. J. & Eaves, A. C. Erythropoietin (Ep) dose-response curves for three classes of erythroid progenitors in normal humanmarrowand in patients with polycythemia vera. Blood, 1978; 52: 1196-210.
223. Gregory, C. J. & Eaves, A. C. Three stages of erythropoietic progenitor cell differentiation distinguished by a number of physical and biologic properties. Blood, 1978; 51: 527-37.
224. Eaves, C. J., Humphries, R. K., & Eaves, A. C. In vitro characterization of erythroid precursor cells and the erythropoietic differentiation process. In G. Stamatoyannopoulos & A.W. Nienhuis, eds., Cellular and Molecular Regulation of Hemoglobin Switching (New York: Grune and Stratton, 1979), pp. 251-73.
225. Koury, M. J. & Bondurant, M. C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science, 1990; 248: 378-81.
226. Stopka, T., Zivny, J. H., Stopkova, P., Prchal, J. F., & Prchal, J. T. Human hematopoietic progenitors express erythropoietin. Blood, 1998; 91: 3766-72.
227. Prchal, J. F. & Axelrad, A. A. Bone marrow responses in polycythemia vera. NEngl J Med, 1974; 290: 1382.
228. Eaves, A. C., Krystal, G., Cashman, J. D., & Eaves, C. J. Polycythemia vera: in vitro analysis of regulatory defects. In E. D. Zanjani, M. Tavassoli, & J. L. Ascensao, eds., Regulation of erythropoiesis (New York: PMA Publishing, 1988), pp. 523-35.
229. Lemoine, F., Najman, A., Baillou, C., et al. A prospective study of the value of bone marrow erythroid progenitor cultures in polycythemia. Blood, 1986; 68: 996-1002.
230. Zwicky, C., Theiler, L., Zbären, K., Ischi, E., & Tobler, A. The predictivevalueofclonogenicstemcellassaysforthediagnosis of polycythaemia vera. Br J Haematol, 2002; 117: 598-604.
231. Zanjani, E. D., Weinberg, R. S., Nomdedeu, B., Kaplan, M. E., & Wasserman, L. R. In vitro assessment of similarities between erythroid precursors of fetal sheep and patients with polycythemia vera. In M. J. Murphy, ed., In Vitro Aspects of Erythropoiesis (Berlin: Springer, 1978), pp. 118-122.
232. Eaves, A. C. & Eaves, C. J. Abnormalities in the erythroid progenitor compartments in patients with chronic myelogenous leukemia (CML). Exp Hematol, 1979; 7: 65-75.
233. Issaad, C. & Vainchenker, W. Growth of erythroid colonies in chronic myelogenous leukemia is independent of erythropoietin only in the presence of steel factor. Blood, 1994; 84: 3447-56.
234. Turhan, A. G., Cashman, J. D., Eaves, C. J., Humphries, R. K., & Eaves, A. C. Variable expression of features of normal and neoplastic stem cells in patients with thrombocytosis. Br J Haematol, 1992; 82: 50-7.
235. Juvonen, E., Ikkala, E., Oksanen, K., & Ruutu, T. Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications. Br J Haematol, 1993; 83: 192-7.
236. Florensa, L., Besses, C., Woessner, S., et al. Endogenous megakaryocyte and erythroid colony formation from blood in essential thrombocythaemia. Leukemia, 1994; 9: 271-3.
237. Griesshammer, M., Klippel, S., Strunck, E., et al. PRV-1 mRNA expression discriminates two types of essential thrombocythemia. Ann Hematol, 2004; 83: 364-70.
238. Nakeff, A. & Daniels-McQueen, S. In vitro colony assay for a new class of megakaryocyte precursor: colony-forming unit megakaryocyte (CFU-M). Proc Soc Exp Biol Med, 1976; 151: 587-90.
239. Ishibashi, T., Miller, S. L., &Burstein, S. A. Type beta transforming growth factor is a potent inhibitor ofmurine megakaryocytopoiesis in vitro. Blood, 1987; 69: 1737-41.
240. Berthier, R., Valiron, O., Scheweitzer, A., & Marguerie, G. Serum-free medium allows the optimal growth of human megakaryocyte progenitors compared with human plasma supplemented cultures: role of TGF-beta. Stem Cells, 1993; 11: 120-9.
241. Hogge, D., Fanning, S., Bockhold, K., et al. Quantitation and characterization of human megakaryocyte colony-forming cells using a standardized serum-free agarose assay. Br J Haematol, 1997; 96: 790-800.
242. Briddell, R. A.&Hoffman, R. Cytokine regulation of the human burst-forming unit-megakaryocyte. Blood, 1990; 76: 516-22.
243. Debili, N., Wendling, F., Katz, A., et al. The Mpl-ligandor thrombopoietin or megakaryocyte growth and differentiative factor has both direct proliferative and differentiative activities on human megakaryocyte progenitors. Blood, 1986; 86: 2516-25.
244. Hoffman, R. Regulation of megakaryocytopoiesis. Blood, 1989; 74: 1196-212.
245. Debili, N., Issaad, C., Masse, J.-M., et al. Expression of CD34 and platelet glycoproteins during human megakaryocytic differentiation. Blood, 1992; 80: 3022-35.
246. Johnson, G. R. & Metcalf, D. Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin. Proc Natl Acad Sci U S A, 1977; 74: 3879-82.
247. Fauser, A. A. &Messner, H. A. Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood. Blood, 1978; 52: 1243-8.
248. Humphries, R. K., Jacky, P. B., Dill, F. J., Eaves, A. C., & Eaves, C. J. CFU-S in individual erythroid colonies derived in vitro from adult mouse marrow. Nature, 1979; 279: 718-20.
249. Holyoake, T. L., Freshney, M. G., Konwalinka, G., et al. Mixed colony formation in vitro by the heterogeneous compartment of multipotential progenitors in human bone marrow. Leukemia, 1993; 7: 207-13.
250. McNiece, I. K., Stewart, F. M., Deacon, D. M., et al. Detection of a human CFC with a high proliferative potential. Blood, 1989; 74: 609-12.
251. Pragnell, I. B., Wright, E. G., Lorimore, S. A., et al. The effect of stem cell proliferation regulators demonstrated with an in vitro assay. Blood, 1988; 72: 196-201.
252. Ogawa, M. Differentiation and proliferation of hematopoietic stem cells. Blood, 1993; 81: 2844-53.
253. Humphries, R. K., Eaves, A. C., &Eaves, C. J. Characterization of a primitive erythropoietic progenitor found in mouse marrow before and after severalweeks in culture. Blood, 1979; 53: 746-63.
254. Nakahata, T. & Ogawa, M. Identification in culture of a class of hemopoietic colony-formingunits with extensive capability to Cambridge Books Online (c) Cambridge University Press, 2009 Anatomy and physiology of hematopoiesis 97 self-renew and generate multipotential hemopoietic colonies. Proc Natl Acad Sci U S A, 1982; 79: 3843-7.
255. Lim, B., Jamal, N., & Messner, H. A. Flexible association of hemopoietic differentiation programs in multilineage colonies. J Cell Physiol, 1984; 121: 291-7.
256. Suda, T., Suda, J., & Ogawa, M. Proliferative kinetics and differentiation of murine blast cell colonies in culture: evidence for variable Go periods and constant doubling rates of early pluripotent hemopoietic progenitors. J Cell Physiol, 1983; 117: 308-18.
257. Leary, A. G., Zeng, H. Q., Clark, S. C., &Ogawa, M. Growthfactor requirements for survival in Go and entry into the cell cycle of primitive human hemopoietic progenitors. Proc Natl Acad Sci U S A, 1992; 89: 4013-17.
258. Leary, A. G. & Ogawa, M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood, 1987; 69: 953-6.
259. Hirayama, F., Shih, J. P., Awgulewitsch, A., et al. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc Natl Acad Sci U S A, 1992; 89: 5907-11.
260. Hirayama, F., Aiba, Y., Ikebuchi, K., Sekiguchi, S., & Ogawa, M. Differentiation in culture of murine primitive lymphohematopoietic progenitors toward T-cell lineage. Blood, 1999; 93: 4187-95.
261. Yonemura, Y., Ku, H., Hirayama, F., Souza, L. M., & Ogawa, M. Interleukin 3 or interleukin 1 abrogates the reconstituting ability of hematopoietic stem cells. Proc Natl Acad Sci U S A, 1996; 93: 4040-4.
262. Buick, R. N., Till, J. E., & McCulloch, E. A. Colony assay for proliferative blast cells circulating in myeloblastic leukemia. Lancet, 1977; 1: 862-3.
263. Moore, M. A. S., Williams, N., &Metcalf, D. In vitro colony formation by normal and leukemic human hematopoietic cells: characterization of the colony-formingcells. J Natl Cancer Inst, 1973; 50: 603-23.
264. Izaguirre, C. A., Minden, M. D., Howatson, A. F., &McCulloch, E. A. Colony formation by normal and malignant human Blymphocytes. Br J Cancer, 1980; 42: 430-7.
265. Izaguirre, C. A., Curtis, J., Messner, H., & McCulloch, E. A. A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia. Blood, 1981; 57: 823-9.
266. Oster, W., Mertelsmann, R., & Herrmann, F. Role of colonystimulating factors in the biology of acute myelogenous leukemia. Int J Cell Cloning, 1989; 7: 13-29.
267. Lowenberg, B. & Touw, I. P. Hematopoietic growth factors and their receptors in acute leukemia. Blood, 1993; 81: 281-92.
268. Drexler, H. G. Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia, 1996; 10: 588-99.
269. Drexler, H. G. & Quentmeier, H. Thrombopoietin: expression of its receptor MPL and proliferative effects on leukemic cells. Leukemia, 1996; 10: 1405-21.
270. Fialkow, P. J., Janssen, J. W. G., & Bartram, C. R. Clonal remissions in acute nonlymphocytic leukemia: evidence for a multistep pathogenesis of the malignancy. Blood, 1991; 77: 1415-17.
271. Tachibana, N., Raimondi, S. C., Lauer, S. J., Sartain, P., & Dow, L. W. Evidence for a multipotential stem cell disease in some childhood Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood, 1987; 70: 1458-61.
272. Secker-Walker, L. M. & Craig, J. M. Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review. Leukemia, 1993; 7: 147-51.
273. Spangrude, G. J., Heimfeld, S., & Weissman, I. L. Purification and characterization of mouse hematopoietic stem cells. Science, 1988; 241: 58-62.
274. Bertoncello, I., Hodgson, G. S., & Bradley, T. R. Multiparameter analysis of transplantable hemopoietic stem cells: I. The separation and enrichment of stem cells homing to marrow and spleen on the basis of Rhodamine-123 fluorescence. Exp Hematol, 1985; 13: 999-1006.
275. Chaudhary, P. M. & Roninson, I. B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell, 1991; 66: 85-94.
276. Zhou, S., Scheutz, J. D., Bunting, K. D., et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med, 2001; 7: 1028-34.
277. Jones, R. J., Barber, J.P., Vala, M.S., et al. Assessmentofaldehyde dehydrogenase in viable cells. Blood, 1995; 85: 2742-6.
278. Storms, R. W., Trujillo, A. P., Springer, J. B., et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci U S A, 1999; 96: 9118-23.
279. Lansdorp, P. M., Dragowska, W., & Mayani, H. Ontogenyrelated changes in proliferative potential of human hematopoietic cells. J Exp Med, 1993; 178: 787-91.
280. Lyons, A. B. & Parish, C. R. Determination of lymphocyte division by flow cytometry. J Immunol Methods, 1994; 171: 131-7.
281. Nordon, R. E., Ginsberg, S. S., &Eaves, C. J. High resolution cell division tracking demonstrates the Flt3-ligand-dependence of human marrow CD34+CD38-cell production in vitro. Br J Haematol, 1997; 98: 528-39.
282. Akashi, K., Traver, D., Miyamoto, T., &Weissman, I. L. A clonogeniccommonmyeloidprogenitor that gives rise to allmyeloid lineages. Nature, 2000; 404: 193-7.
283. Nakorn, T. N., Traver, D., Weissman, I. L., & Akashi, K. Myeloerythroid-restricted progenitors are sufficient to confer radioprotectionandprovide the majority of day 8 CFU-S. J Clin Invest, 2002; 109: 1579-85.
284. Manz, M. G., Miyamoto, T., Akashi, K., & Weissman, I. L. Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci U S A, 2002; 99: 11872-7.
285. Sauvageau, G., Lansdorp, P. M., Eaves, C. J., et al. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc Natl Acad Sci U S A, 1994; 91: 12223-7.
286. Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., & Mulligan, R. C. Isolation and functional properties of murine hematopoieticstemcells that are replicating in vivo. J Exp Med, 1996; 183: 1797-806.
287. Krause, D. S., Fackler, M. J., Civin, C. I., & May, W. S. CD34: structure, biology, and clinical utility. Blood, 1996; 87: 1-13.
288. Krause, D. S., Ito, T., Fackler, M. J., et al. Characterization of murine CD34, amarker forhematopoieticprogenitorandstem cells. Blood, 1994; 84: 691-701.
289. Morel, F., Szilvassy, J., Travis, M., Chen, B., & Galy, A. Primitive hematopoietic cells in murine bone marrowexpress the CD34 antigen. Blood, 1996; 88: 3774-84.
290. Bhatia, M., Wang, J. C. Y., Kapp, U., Bonnet, D., & Dick, J. E. Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A, 1997; 94: 5320-5.
291. Kawano, Y., Takaue, Y., Watanabe, A., et al. Partially mismatched pediatric transplants with allogeneic CD34(+) blood cells from a related donor. Blood, 1998; 92: 3123-30.
292. Michallet, M., Philip, T., Philip, I., et al. Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiplemyeloma: impact of HSC dose on engraftment, safety, and immune reconstitution. Exp Hematol, 2000; 28: 858-70.
293. Negrin, R. S., Atkinson, K., Leemhuis, T., et al. Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with metastatic breast cancer. Biol Blood Marrow Transplant, 2000; 6: 262-71.
294. Fujisaki, T., Berger, M.G., Rose-John, S., &Eaves, C. J. Rapid differentiation of a rare subset of adult human lin-CD34-CD38-cells stimulated by multiple growth factors in vitro. Blood, 1999; 94: 1926-32.
295. Storms, R. W., Goodell, M. A., Fisher, A., Mulligan, R. C., & Smith, C. Hoechst dye efflux reveals a novel CD7+ CD34-lymphoid progenitor in human umbilical cord blood. Blood, 2000; 96: 2125-33.
296. Zanjani, E. D., Almeida-Porada, G., Livingston, A. G., Zeng, H., & Ogawa, M. Reversible expression of CD34 by adult human bone marrow long-term engrafting hematopoietic stem cells. Exp Hematol, 2003; 31: 406-12.
297. Okuno, Y., Iwasaki, H., Huettner, C. S., et al. Differential regulation of the human and murine CD34 genes in hematopoietic stem cells. Proc Natl Acad Sci U S A, 2002; 99: 6246-51.
298. Radomska, H. S., Gonzalez, D. A., Okuno, Y., et al. Transgenic targeting with regulatory elements of the human CD34 gene. Blood, 2002; 100: 4410-19.
299. Deaglio, S., Mehta, K., & Malavasi, F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk Res, 2001; 25: 1-12.
300. Tajima, F., Deguchi, T., Laver, J. H., Zeng, H., & Ogawa, M. Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells. Blood, 2001; 97: 2618-24.
301. Higuchi, Y., Zeng, H., & Ogawa, M. CD38 expression by hematopoietic stem cells of newborn and juvenile mice. Leukemia, 2003; 17: 171-4.
302. Terstappen, L. W. M. M., Huang, S., Safford, M., Lansdorp, P. M., & Loken, M. R. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38-progenitor cells. Blood, 1991; 77: 1218-27.
303. Hao, Q.-L. H., Shah, A. J., Thiemann, F.T., Smogorzewska, E. M., & Crooks, G. M. A functional comparison of CD34+CD38-cells in cord blood and bone marrow. Blood, 1995; 86: 3745-53.
304. Nicolini, F. E., Imren, S., Oh, I.-H., et al. Expression of a human beta-globin transgene in erythroid cells derived from retrovirally transduced transplantable human fetal liver and cord blood cells. Blood, 2002; 100: 1257-64.
305. Dorrell, C., Gan, O. I., Pereira, D. S., Hawley, R. G., & Dick, J. E. Expansion of human cord blood CD34+CD38-cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function. Blood, 2000; 95: 102-10.
306. Zhou, S., Morris, J. J., Barnes, Y., Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A, 2002; 99: 12 339-44.
307. Scharenberg, C.W., Harkey, M.A., &Torok-Storb, B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood, 2002; 99: 507-12.
308. Goodell, M. A., Rosenzweig, M., Kim, H., et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med, 1997; 3: 1337-45.
309. Feuring-Buske, M. &Hogge, D. E. Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34+CD38-progenitor cells from patients with acute myeloid leukemia. Blood, 2001; 97: 3882-9.
310. Gussoni, E., Soneoka, Y., Strickland, C. D., et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature, 1999; 401: 390-4.
311. Murayama, A., Matsuzaki, Y., Kawaguchi, A., Shimazaki, T., & Okano, H. Flow cytometric analysis of neural stem cells in the developing and adult mouse brain. J Neurosci Res, 2002; 69: 837-47.
312. Bhattacharya, S., Jackson, J. D., Das, A. V., et al. Direct identification and enrichment of retinal stem cells/progenitors by Hoechst dye efflux assay. Invest Ophthalmol Vis Sci, 2003; 44: 2764-73.
313. Hierlihy, A. M., Seale, P., Lobe, C. G., Rudnicki, M. A., & Megeney, L. A. The post-natal heart contains a myocardial stem cell population. FEBS Lett, 2002; 530: 239-43.
314. Asakura, A.&Rudnicki, M.A. Sidepopulationcells fromdiverse adult tissues are capable of in vitro hematopoietic differentiation. Exp Hematol, 2002; 30: 1339-45.
315. Issarachai, S., Priestley, G. V., Nakamoto, B., & Papayannopoulou, T. Cells with hemopoietic potential residing inmuscle are itinerant bone marrow-derived cells. Exp Hematol, 2002; 30: 366-73.
316. Morrison, S. J., Wright, D. E., & Weissman, I. L. Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization. Proc Natl Acad Sci U S A, 1997; 94: 1908-13.
317. Jordan, C. T., McKearn, J. P., & Lemischka, I. R. Cellular and developmental properties of fetal hematopoietic stem cells. Cell, 1990; 61: 953-63.
318. Ortiz, M., Wine, J. W., Lohrey, N., et al. Functional characterization of a novel hematopoietic stem cell and its place in the c-kit maturation pathway in bone marrow cell development. Immunity, 1999; 10: 173-82.
319. Christensen, J. L. & Weissman, I. L. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-termstem cells. Proc Natl Acad SciUS A, 2001; 98: 14 541-6.
320. Adolfsson, J., Borge, O. J., Bryder, D., et al. Upregulation of flt3 expression within the bone marrow Lin-Sca1+c-kit+ stem cell compartment is accompanied by loss of self-renewal capacity. Immunity, 2001; 15: 659-69.
321. Hasumura, M., Imada, C., & Nawa, K. Expression change of Flk-2/Flt-3 on murine hematopoietic stem cells in activating state. Exp Hematol, 2003; 31: 1331-7.
322. Huang, S. & Terstappen, L. W. M. M. Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38-hematopoietic stem cells. Blood, 1994; 83: 1515-26.
323. Miller, J. S., McCullar, V., & Verfaillie, C. M. Ex vivo culture of CD34+/Lin-/DR-cells in stroma-derived soluble factors, interleukin-3, and macrophage inflammatory protein 1-alpha maintains not only myeloid but also lymphoid progenitors in a novel switch culture assay. Blood, 1998; 91: 4516-22.
324. Traycoff, C. M., Abboud, M. R., Laver, J., et al. Evaluation of the in vitro behavior of phenotypically defined populations of umbilical cord blood hematopoietic progenitor cells. Exp Hematol, 1994; 22: 215-22.
325. Debili, N., Robin, C., Schiavon, V., et al. Different expression of CD41 on human lymphoid and myeloid progenitors from adults and neonates. Blood, 2001; 97: 2023-30.
326. Lander, E. S., Linton, L. M., Birren, B., et al. Initial sequencing and analysis of the human genome. Nature, 2001; 409: 860-921.
327. Venter, J. C., Adams, M. D., Myers, E.W., et al. The sequence of the human genome. Science, 2001; 291: 1304-51.
328. Waterston, R. H., Lindblad-Toh, K., Birney, E., et al. Initial sequencing and comparative analysis of the mouse genome. Nature, 2002; 420: 520-62.
329. Brady, G., Billia, F., Knox, J., et al. Analysis of gene expression in a complex differentiation hierarchy by global amplification of cDNA from single cells. Curr Biol, 1995; 5: 909-22.
330. Cheng, T., Shen, H., Giokas, D., et al. Temporal mapping of gene expression levels during the differentiation of individual primary hematopoietic cells. Proc Natl Acad Sci U S A, 1996; 93: 13158-63.
331. Zinovyeva, M. V., Mark, J., Zijlmans, J. M., et al. Analysis of gene expression in subpopulations of murine hematopoietic stem and progenitor cells. Exp Hematol, 2000; 28: 318-34.
332. Oh, I.-H., Lau, A., & Eaves, C. J. During ontogeny primitive (CD34+CD38-) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts. Blood, 2000; 96: 4160-8.
333. Phillips, R. L., Ernst, R. E., Brunk, B., et al. The genetic program of hematopoietic stem cells. Science, 2000; 288: 1635-40.
334. Billia, F., Barbara, M., McEwen, J., Trevisan, M., & Iscove, N. N. Resolution of pluripotential intermediates in murine hematopoietic differentiation by global complementary DNA amplification from single cells: confirmation of assignments by expression profiling of cytokine receptor transcripts. Blood, 2001; 97: 2257-68.
335. Ivanova, N.B., Dimos, J.T., Schaniel, C., et al. Astemcell molecular signature. Science, 2002; 298: 601-4.
336. Akashi, K., He, X., Chen, J., et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood, 2003; 101: 383-90.
337. Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C., & Melton, D. A. "Stemness": transcriptional profiling of embryonic and adult stem cells. Science, 2002; 298: 597-600.
338. Terskikh, A.V., Easterday, M.C., Li, L., et al. Fromhematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci U S A, 2001; 98: 7934-9.
339. Hu, M., Krause, D., Greaves, M., et al. Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev, 1997; 11: 774-85.
340. Delassus, S., Titley, I., & Enver, T. Functional and molecular analysis of hematopoietic progenitors derived from the aortagonad-mesonephros region of the mouse embryo. Blood, 1999; 94: 1495-503.
341. Bruno, L., Hoffmann, R., McBlane, F., et al. Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. Mol Cell Biol, 2004; 24: 741-56.
342. Miyamoto, T., Iwasaki, H., Reizis, B., et al. Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell, 2002; 3: 137-47.
343. Ye, M., Iwasaki, H., Laiosa, C. V., et al. Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential. Immunity, 2003; 19: 689-99.
344. Eschbach, J.W., Abdulhadi, M.H., Browne, J. K., et al. Recombinant human erythropoietin in anemic patients with end-stage renal disease: results of a Phase III multicenter clinical trial. Ann Intern Med, 1989; 111: 992-1000.
345. Packham, G. Mutation of BCL-2 family proteins in cancer. Apoptosis, 1998; 3: 75-82.
346. Stirewalt, D. L.&Radich, J.P. Therole of FLT3inhaematopoietic malignancies. Nat Rev Cancer, 2003; 3: 650-65.
347. Lutterbach, B. & Hiebert, S.W. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene, 2000; 245: 223-35.
348. Robb, L. & Begley, C. G. The SCL/TAL1 gene: roles in normal and malignant haematopoiesis. Bioessays, 1997; 19: 607-13.
349. Goldman, J. M. & Melo, J. V. Chronic myeloid leukemia-advances in biology and new approaches to treatment. NEngl J Med, 2003; 349: 1451-64.
350. Williams, G.T.&Smith, C. A. Molecular regulation of apoptosis: genetic controls on cell death. Cell, 1993; 74: 777-9.
351. Wickremasinghe, R. G. & Hoffbrand, A. V. Biochemical and genetic control of apoptosis: relevance to normal hematopoiesis and hematological malignancies. Blood, 1999; 93: 3587-600.
352. Barisic, K., Petrik, J., & Rumora, L. Biochemistry of apoptotic cell death. Acta Pharm, 2003; 53: 151-64.
353. Peters, R., Leyvraz, S., &Perey, L. Apoptotic regulation in primitive hematopoietic precursors. Blood, 1998; 92: 2041-52.
354. Veis, D. J., Sorenson, C. M., Shutter, J. R., &Korsmeyer, S. J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell, 1993; 75: 229-40.
355. Nakayama, K. I., Nakayama, K., Negishi, I., et al. Disappearance of the lymphoid system in Bcl-2homozygous mutant chimeric mice. Science, 1993; 261: 1584-8.
356. Bouillet, P., Metcalf, D., Huang, D. C., et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science, 1999; 286: 1735-8.
357. Motoyama, N., Kimura, T., Takahashi, T., Watanabe, T., & Nakano, T. Bcl-× prevents apoptotic cell death of both primitive and definitive erythrocytes at the end of maturation. J Exp Med, 1999; 189: 1691-8.
358. Hamasaki, A., Sendo, F., Nakayama, K., et al. Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene. J Exp Med, 1998; 188: 1985-92.
359. Sherr, C. J. & Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev, 1999; 13: 1501-12.
360. Jones, S. M. & Kazlauskas, A. Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat Cell Biol, 2001; 3: 165-72.
361. Bartek, J. & Lukas, J. p27 destruction: Cks1 pulls the trigger. Nat Cell Biol, 2001; 3: E95-98.
362. Della, R. F., Borriello, A., Mastropietro, S., et al. Expression of G1-phase cell cycle genes during hematopoietic lineage. Biochem Biophys Res Commun, 1997; 231: 73-6.
363. Bassini, A., Pierpaoli, S., Falcieri, E., et al. Selective modulation of the cyclin B/CDK1 and cyclin D/CDK4 complexes during in vitro human megakaryocyte development. Br J Haematol, 1999; 104: 820-8.
364. Yaroslavskiy, B., Watkins, S., Donnenberg, A. D., Patton, T. J., & Steinman, R. A. Subcellular and cell-cycle expression profiles of CDK-inhibitors in normal differentiatingmyeloid cells. Blood, 1999; 93: 2907-17.
365. Taniguchi, T., Endo, H., Chikatsu, N., et al. Expression of p21Cip1/Waf1/Sdi1 and p27Kip1 cyclin-dependent kinase inhibitors during human hematopoiesis. Blood, 1999; 93: 4167-78.
366. Hsieh, F. F., Barnett, L. A., Green, W. F., et al. Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27(Kip1) and inactivation of cdk2 kinase. Blood, 2000; 96: 2746-54.
367. Cheng, T., Rodrigues, N., Shen, H., et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science, 2000; 287: 1804-8.
368. Cheng, T., Rodrigues, N., Dombkowski, D., Stier, S., & Scadden, D. T. Stem cell repopulation efficiency but not pool size is governed by p27kip1. Nat Med, 2000; 6: 1235-40.
369. Zandstra, P.W., Conneally, E., Petzer, A. L., Piret, J. M., & Eaves, C.J. Cytokinemanipulationofprimitivehumanhematopoietic cell self-renewal. Proc Natl Acad SciUS A, 1997; 94: 4698-703.
370. Matsunaga, T., Kato, T., Miyazaki, H., & Ogawa, M. Thrombopoietin promotes the survival of murine hematopoietic long-termreconstituting cells: comparison with the effects of FLT3/FLK-2 ligand and interleukin-6. Blood, 1998; 92: 452-61.
371. Borge, O. J., Ramsfjell, V., Cui, L., & Jacobsen, S. E. W. Ability of early acting cytokines to directly promote survival and suppress apoptosis of human primitive CD34+CD38-bone marrow cells with multilineage potential at the single-cell level: key role of thrombopoietin. Blood, 1997; 90: 2282-92.
372. Sitnicka, E., Lin, N., Priestley, G. V., et al. The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells. Blood, 1996; 87: 4998-5005.
373. Li, C. L. & Johnson, G. R. Stem cell factor enhances the survival but not the self-renewal of murine hematopoietic long-term repopulating cells. Blood, 1994; 84: 408-14.
374. Takatoku, M., Sellers, S., Agricola, B. A., et al. Avoidance of stimulation improves engraftment of cultured and retrovirally transducedhematopoieticcells in primates. J Clin Invest, 2001; 108: 447-55.
375. Fauser, A. A. & Messner, H. A. Proliferative state of human pluripotent hemopoietic progenitors(CFU-GEMM)in normal individualsandunder regenerative conditions afterbonemarrow transplantation. Blood, 1979; 54: 1197-200.
376. Jordan, C. T., Yamasaki, G., & Minamoto, D. High-resolution cell cycle analysis of defined phenotypic subsets within primitive human hematopoietic cell populations. Exp Hematol, 1996; 24: 1347-55.
377. Berardi, A. C., Wang, A., Levine, J. D., Lopez, P., & Scadden, D. T. Functional isolation and characterization of human hematopoietic stem cells. Science, 1995; 267: 104-8.
378. Gothot, A., Loo, J. C. M. Van der, Clapp, W., & Srour, E. F. Cell cycle-related changes in repopulating capacity of human mobilized peripheral blood CD34+cells in non-obese diabetic/severe combined immune-deficient mice. Blood, 1998; 92: 2641-9.
379. Bradford, G. B., Williams, B., Rossi, R., & Bertoncello, I. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol, 1997; 25: 445-53.
380. Cheshier, S. H., Morrison, S. J., Liao, X., &Weissman, I. L. In vivo proliferation and cell cycle kinetics of long-termself-renewing Cambridge Books Online (c) Cambridge University Press, 2009 Anatomy and physiology of hematopoiesis 101 hematopoietic stem cells. Proc Natl Acad Sci U S A, 1999; 96: 3120-5.
381. Mahmud, N., Devine, S. M., Weller, K. P., et al. The relative quiescence of hematopoietic stem cells in nonhuman primates. Blood, 2001; 97: 3061-8.
382. Rufer, N., Brummendorf, T. H., Kolvraa, S., et al. Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med, 1999; 190: 157-67.
383. Gordon, M.Y., Riley, G.P., Watt, S. M., &Greaves, M.F. Compartmentalization of a haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone marrow microenvironment. Nature, 1987; 326: 403-5.
384. Roberts, R., Gallagher, J., Spooncer, E., et al. Heparan sulphate bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature, 1988; 332: 376-8.
385. Anderson, D.M., Lyman, S.D., Baird, A., et al. Molecularcloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell, 1990; 63: 235-43.
386. Flanagan, J. G., Chan, D. C., & Leder, P. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the SId mutant. Cell, 1991; 64: 1025-35.
387. Rettenmier, C. W., Roussel, M. F., Ashmun, R. A., et al. Synthesis of membrane-bound colony-stimulating factor 1 (CSF-1) and downmodulation of CSF-1 receptors in NIH 3T3 cells transformed by cotransfection of the human CSF-1 and c-fms (CSF-1 receptor) genes. Mol Cell Biol, 1987; 7: 2378-87.
388. Stein, J., Borzillo, G.V., &Rettenmier, C.W. Direct stimulation of cells expressing receptors for macrophage colony-stimulating factor (CSF-1) by a plasma membrane-bound precursor of human CSF-1. Blood, 1990; 76: 1308-14.
389. Gidali, J. & Lajtha, L. G. Regulation of haemopoietic stem cell turnover in partially irradiated mice. Cell Tissue Kinet, 1972; 5: 147-57.
390. McCulloch, E. A., Siminovitch, L., Till, J. E., Russell, E. S., & Bernstein, S. E. Thecellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl/Sld. Blood, 1965; 26: 399-410.
391. Graham, G. J., Wright, E. G., Hewick, R., et al. Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Nature, 1990; 344: 442-4.
392. Broxmeyer, H. E., Sherry, B., Lu, L., et al. Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells. Blood, 1990; 76: 1110-16.
393. Quesniaux, V. F. J., Graham, G. J., Pragnell, I., et al. Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1a on long-termreconstituting stem cells in vivo. Blood, 1993; 81: 1497-504.
394. Eaves, C. J., Cashman, J. D., Wolpe, S. D., & Eaves, A. C. Unresponsiveness of primitive chronic myeloid leukemia cells to macrophage inflammatory protein 1 alpha, an inhibitor of primitive normal hematopoietic cells. Proc Natl Acad SciUSA, 1993; 90: 12015-9.
395. Cashman, J. D., Clark-Lewis, I., Eaves, A. C., & Eaves, C. J. Differentiation stage-specific regulation of primitive human hematopoietic progenitor cycling by exogenous and endogenous inhibitors in an in vivo model. Blood, 1999; 94: 3722-9.
396. Cashman, J. D., Eaves, C. J., Sarris, A. H., & Eaves, A. C. MCP-1, not MIP-1alpha is the endogenous chemokine that cooperates with TGF-beta to inhibit the cycling of primitive normal but not leukemic (CML) progenitors in long-termhuman marrow cultures. Blood, 1998; 92: 2338-44.
397. Cashman, J., Clark-Lewis, I., Eaves, A., & Eaves, C. Stromalderived factor 1 inhibits the cycling of very primitive human hematopoietic cells in vitro and in NOD/SCID mice. Blood, 2002; 99: 792-9.
398. Cashman, J., Dykstra, B., Clark-Lewis, I., Eaves, A., & Eaves, C. Changes in the proliferative activity of human hematopoietic stem cells in NOD/SCIDmiceandenhancement of their transplantability after in vivo treatment with cell cycle inhibitors. J Exp Med, 2002; 196: 1141-9.
399. Glimm, H., Tang, P., Clark-Lewis, I., Kalle, C. von, & Eaves, C. Ex vivo treatment of proliferatinghumancord blood stem cells with stroma-derived factor-1 enhances their ability to engraft NOD/SCID mice. Blood, 2002; 99: 3454-7.
400. Till, J. E., McCulloch, E. A., & Siminovitch, L. A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci U S A, 1964; 51: 29-36.
401. Vogel, H., Niesisch, H., & Matioli, G. The self-renewal probability of haemopoietic stem cells. J Cell Physiol, 1968; 72: 221.
402. Till, J. E. & McCulloch, E. A. Hemopoietic stem cell differentiation. Biochim Biophys Acta, 1980; 605: 431-59.
403. Humphries, R. K., Eaves, A. C., & Eaves, C. J. Expression of stem cell behaviour during macroscopic burst formation in vitro. In S. J. Baum, G. D. Ledney, & D. W. van Bekkum, eds., Experimental Hematology Today (New York: Karger, 1980), pp. 39-46.
404. Nakahata, T., Gross, A. J., & Ogawa, M. A stochastic model of self-renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture. J Cell Physiol, 1982; 113: 455-8.
405. Eaves, C., Miller, C., Conneally, E., et al. Introduction to stem cell biology in vitro: threshold to the future. Ann NYAcad Sci, 1999; 872: 1-8.
406. Iscove, N. N.&Nawa, K. Hematopoietic stem cells expand during serial transplantation in vivo without apparent exhaustion. Curr Biol, 1997; 7: 805-8.
407. Thorsteinsdottir, U., Sauvageau, G., & Humphries, R. K. Enhancedin vivoregenerative potential of HOXB4-transduced hematopoietic stem cells with regulation of their pool size. Blood, 1999; 94: 2605-12.
408. Pineault, N., Helgason, C. D., Lawrence, H. J., & Humphries, R. K. Differential expression of Hox, Meis1 and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp Hematol, 2002; 30: 49-57.
409. Lessard, J., Baban, S., & Sauvageau, G. Stage-specific expression of Polycomb group genes in human bone marrow cells. Blood, 1998; 91: 1216-24.
410. Park, I. K., Qian, D., Kiel, M., et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature, 2003; 423: 302-5.
411. Sauvageau, G., Thorsteinsdottir, U., Eaves, C. J., et al. Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Dev, 1995; 9: 1753-65.
412. Buske, C., Feuring-Buske, M., Abramovich, C., et al. Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells. Blood, 2002; 100: 862-8.
413. Antonchuk, J., Sauvageau, G., & Humphries, R. K. HoxB4-induced expansion of adult hematopoietic stem cells ex vivo. Cell, 2002; 109: 39-45.
414. Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature, 2003; 423: 255-60.
415. Krosl, J., Austin, P., Beslu, N., et al. In vitro expansion of hematopoietic stem cells by recombinant TAT-HOXB4 protein. Nat Med, 2003; 9: 1428-32.
416. Tsuji, K., Lyman, S. D., Sudo, T., Clark, S. C., & Ogawa, M. Enhancement of murine hematopoiesis by synergistic interactions between Steel factor (ligand for c-kit), Interleukin-11, and other early acting factors in culture. Blood, 1992; 79: 2855-60.
417. Yonemura, Y., Ku, H., Lyman, S.D., &Ogawa, M. In vitro expansion of hematopoietic progenitors and maintenance of stem cells: comparison between Flt3/Flk-2 ligand and kit ligand. Blood, 1997; 89: 1915-21.
418. Ueda, T., Tsuji, K., Yoshino, H., et al. Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor. J Clin Invest, 2001; 105: 1013-21.
419. Ramsfjell, V., Borge, O. J., Veiby, O.P., et al. Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitivemurinebonemarrowprogenitor cells insynergywith early acting cytokines: distinct interactions with the ligands for c-kit and FLT3. Blood, 1996; 88: 4481-92.
420. Ku, H., Yonemura, Y., Kaushansky, K., & Ogawa, M. Thrombopoietin, the ligand for the Mplreceptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice. Blood, 1996; 87: 4544-51.
421. Petzer, A. L., Zandstra, P. W., Piret, J. M., & Eaves, C. J. Differential cytokine effects on primitive (CD34+CD38-) human hematopoietic cells: novel responses to flt3-ligand and thrombopoietin. J Exp Med, 1996; 183: 2551-8.
422. Ebihara, Y., Wada, M., Ueda, T., et al. Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38-cells expressing Flk2/Flt3. Br J Haematol, 2002; 119: 525-34.
423. Sitnicka, E., Buza-Vidas, N., Larsson, S., et al. Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells. Blood, 2003; 102: 881-6.
424. Murdoch, B., Chadwick, K., Martin, M., et al. Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo. Proc Natl Acad Sci U S A, 2003; 100: 3422-7.
425. Cobas, M., Wilson, A., Ernst, B., et al. _-catenin is dispensable for hematopoiesis and lymphopoiesis. J Exp Med, 2004; 199: 221-9.
426. Bryder, D., Ramsfjell, V., Dybedal, I., et al. Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by fas and tumor necrosis factor receptor activation. J Exp Med, 2001; 194: 941-52.
427. Dybedal, I., Bryder, D., Fossum, A., Rusten, L. S., & Jacobsen, S. E. Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells. Blood, 2001; 98: 1782-91.
428. Shivdasani, R. A. & Orkin, S. H. The transcriptional control of hematopoiesis. Blood, 1996; 87: 4025-39.
429. Tenen, D. G., Hromas, R., Licht, J.D., &Zhang, D. Transcription factors, normal myeloid development and leukemia. Blood, 1997; 90: 489-519.
430. Nutt, S. L., Heavey, B., Rolink, A. G., & Busslinger, M. Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature, 1999; 401: 556-62.
431. Westin, E. H., Gallo, R. C., Arya, S. K., et al. Differential expression of the amv gene in human hematopoietic cells. Proc Natl Acad Sci U S A, 1982; 79: 2194-8.
432. Gonda, T. J.&Metcalf, D. Expression ofmyb, mycandfos protooncogenes during the differentiation of a murine myeloid leukaemia. Nature, 1984; 310: 249-51.
433. Sheiness, D. & Gardinier, M. Expression of a proto-oncogene (proto-myb) in hemopoietic tissues of mice. Mol Cell Biol, 1984; 4: 1206-12.
434. Buske, C.&Humphries, R. K. Homeobox genesinleukemogenesis. Int J Hematol, 2000; 71: 301-8.
435. Lawrence, H. J., Sauvageau, G., Largman, C., & Humphries, R. K. Homeobox gene networks and the regulation of hematopoiesis. In L. I. Zon, ed., Hematopoiesis: A Developmental Approach (New York: Oxford University Press, 2001), pp. 402-14.
436. Katzav, S., Martin-Zanca, D., & Barbacid, M. Vav, a novel humanoncogene derived froma locus ubiquitously expressed in hematopoetic cells. EMBO J, 1989; 8: 2283-90.
437. Adams, J. M., Houston, H., Allen, J., Lints, T., & Harvey, R. The hematopoietically expressed vav proto-oncogene shares homology with the dblGDP-GTPexchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization. Oncogene, 1992; 7: 611-18.
438. Wagner, J. E., Collins, D., Fuller, S., et al. Isolation of small, primitive human hematopoietic stem cells: distribution of Cambridge Books Online (c) Cambridge University Press, 2009 Anatomy and physiology of hematopoiesis 103 cell surface cytokine receptors and growth in SCID-Hu mice. Blood, 1995; 86: 512-23.
439. Testa, U., Fossati, C., Samoggia, P., et al. Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors. Blood, 1996; 88: 3391-406.
440. McKinstry, W. J., Li, C. L., Rasko, J. E. J., et al. Cytokine receptor expressiononhematopoietic stemandprogenitor cells. Blood, 1997; 89: 65-71.
441. Helgason, C. D., Damen, J. E., Rosten, P., et al. Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev, 1998; 12: 1610-20.
442. Voura, E. B., Billia, F., Iscove, N. N., & Hawley, R. G. Expression mapping of adhesion receptor genes during differentiation of individual hematopoietic precursors. Exp Hematol, 1997; 25: 1172-9.
443. Mucenski, M. L., McLain, K., Kier, A. B., et al. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell, 1991; 65: 677-89.
444. Pevny, L., Simon, M. C., Robertson, E., et al. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature, 1991; 349: 257-60.
445. Georgopoulos, K., Moore, D. D., & Derfler, B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science, 1992; 258: 808-12.
446. Georgopoulos, K., Bigby, M., Wang, J. H., et al. Early arrest in lymphocyte differentiation in Ikaros mutant mice. Cell, 1994; 78: 143-56.
447. Scott, E.W., Simon, M. C., Anastasi, J., &Singh, H. Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science, 1994; 265: 1573-7.
448. Urbanek, P., Wang, Z.-Q., Fetka, I., Wagner, E. F., & Busslinger, M. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell, 1994; 79: 901-12.
449. Olson, M. C., Scott, E.W., Hack, A. A., et al. PU.1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation. Immunity, 1995; 3: 703-14.
450. Robb, L., Elwood, N. J., Elefanty, A. G., et al. The scl gene is required for the generation of all hematopoietic lineages in the adult mouse. EMBO J, 1996; 15: 4123-9.
451. Porcher, C., Swat, W., Rockwell, K., et al. The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell, 1996; 86: 47-57.
452. Okuda, T., Deursen, J. van, Hiebert, S.W., Grosveld, G., &Downing, J. R. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell, 1996; 84: 321-30.
453. Sasaki, K., Yagi, H., Bronson, R. T., et al. Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta. Proc Natl Acad Sci U S A, 1996; 93: 12 359-63.
454. Wang, Q., Stacy, T., Binder, M., et al. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous systemandblocks definitive hematopoiesis. Proc Natl Acad Sci U S A, 1996; 93: 3444-9.
455. Hendriks, R. W., Nawijn, M. C., Engel, J. D., et al. Expression of the transcription factor GATA-3 is required for the development of the earliest T cell progenitors and correlates with stages of cellular proliferation in the thymus. Eur J Immunol, 1999; 29: 1912-18.
456. Valtieri, M., Tocci, A., Gabbianelli, M., et al. Enforced TAL-1 expression stimulates primitive, erythroid and megakaryocytic progenitors but blocks the granulopoietic differentiation program. Cancer Res, 1998; 58: 562-9.
457. Iwasaki, H., Mizuno, S., Wells, R. A., et al. GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity, 2003; 19: 451-62.
458. Thorsteinsdottir, U., Sauvageau, G., Hough, M. R., et al. Overexpression ofHOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol, 1997; 17: 495-505.
459. Sauvageau, G., Thorsteinsdottir, U., Hough, M. R., et al. Overexpression of HOXB3 in hematopoietic cells causes defective lymphoid development and progressive myeloproliferation. Immunity, 1997; 6: 13-22.
460. Kulessa, H., Frampton, J., Graf, T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev, 1995; 9: 1250-62.
461. Thorsteinsdottir, U., Mamo, A., Kroon, E., et al. Overexpression of the myeloid leukemia-associated Hoxa9 gene in bone marrow cells induces stem cell expansion. Blood, 2002; 99: 121-9.
462. Taghon, T., Stolz, F., De Smedt, M., et al. HOX-A10 regulates hematopoietic lineage commitment: evidence for a monocyte-specific transcription factor. Blood, 2002; 99: 1197-204.
463. Hirasawa, R., Shimizu, R., Takahashi, S., et al. Essential and instructive roles of GATA factors in eosinophil development. J Exp Med, 2002; 195: 1379-86.
464. Cantor, A. B. & Orkin, S. H. Hematopoietic development: a balancing act. Curr Opin Genet Dev, 2001; 11: 513-19.
465. Rolink, A. G., Nutt, S. L., Melchers, F., & Busslinger, M. Longterm in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors. Nature, 1999; 401: 603-6.
466. Nerlov, C., Querfurth, E., Kulessa, H., & Graf, T. GATA-1 interacts with the myeloid PU.1 transcription factor and represses PU.1-dependent transcription. Blood, 2000; 95: 2543-51.
467. Zhang, P., Behre, G., Pan, J., et al. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc Natl Acad Sci U S A, 1999; 96: 8705-10.
468. Rekhtman, N., Radparvar, F., Evans, T., & Skoultchi, A. I. Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes Dev, 1999; 13: 1398-411.
469. Querfurth, E., Schuster, M., Kulessa, H., et al. Antagonism between C/EBPbeta and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors. Genes Dev, 2000; 14: 2515-25.
470. Wu, A.M., Siminovitch, L., Till, J. E., &McCulloch, E. A. Evidence for a relationship between mouse hemopoietic stem cells and cells formingcolonies in culture. Proc Natl Acad SciUSA, 1968; 59: 1209-15.
471. Suda, T., Suda, J., & Ogawa, M. Disparate differentiation in mouse hemopoietic colonies derived frompaired progenitors. Proc Natl Acad Sci U S A, 1984; 81: 2520-4.
472. Takano, H., Ema, H., Sudo, K., & Nakauchi, H. Asymmetric divisionandlineagecommitmentat the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs. J Exp Med, 2004; 199: 295-302.
473. Pharr, P. N., Ogawa, M., Hofbauer, A., &Longmore, G.D. Expression of an activated erythropoietin or a colony-stimulating factor 1 receptor by pluripotent progenitors enhances colony formation but does not induce differentiation. Proc Natl Acad Sci U S A, 1994; 91: 7482-6.
474. Goldsmith, M. A., Mikami, A., You, Y., et al. Absence of cytokine receptor-dependentspecificity in redbloodcell differentiation in vivo. Proc Natl Acad Sci USA, 1998; 95: 7006-11.
475. Stoffel, R., Ziegler, S., Ghilardi, N., et al. Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo. Proc Natl Acad Sci U S A, 1999; 96: 698-702.
476. Dexter, T. M., Heyworth, C. M., Spooncer, E., & Ponting, I. L.O. The role of growth factors in self-renewal and differentiation of haemopoietic stem cells. Philos Trans R Soc Lond B Biol Sci, 1990; 327: 85-98.
477. Borzillo, G. V., Ashmun, R. A., & Sherr, C. J. Macrophage lineageswitchingofmurineearlypre-Blymphoidcellsexpressing transduced fms genes. Mol Cell Biol, 1990; 10: 2703-14.
478. Martin, M., Strasser, A., Baumgarth, N., et al. A novel cellular model (SPGM 1) of switching between the pre-B cell and myelomonocytic lineages. J Immunol, 1993; 150: 4395-406.
479. Klinken, S. P., Alexander, W. S., & Adams, J. M. Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. Cell, 1988; 53: 857-67.
480. Kondo, M., Scherer, D. C., Miyamoto, T., et al. Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines. Nature, 2000; 407: 383-6.
481. Fukunaga, R., Ishizaka-Ikeda, E., & Nagata, S. Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte colony-stimulating factor receptor. Cell, 1993; 74: 1079-87.
482. Metcalf, D. Clonal analysis of proliferation and differentiation of paired daughter cells: action of granulocyte-macrophage colony-stimulating factor on granulocyte-macrophage precursors. Proc Natl Acad Sci U S A, 1980; 77: 5327-30.
483. Metcalf, D. & Burgess, A. W. Clonal analysis of progenitor cell commitment to granulocyte or macrophage production. J Cell Physiol, 1982; 111: 275-83.
484. Metcalf, D. Lineage commitment in the progeny of murine hematopoietic preprogenitor cells: influence of thrombopoietin and interleukin 5. Proc Natl Acad Sci U S A, 1998; 95: 6408-12.
485. Campbell, K. H., McWhir, J., Ritchie, W. A., &Wilmut, I. Sheep cloned by nuclear transfer from a cultured cell line. Nature, 1996; 380: 64-6.
486. Orlic, D., Kajstura, J., Chimenti, S., et al. Bone marrow cells regenerate infarcted myocardium. Nature, 2001; 410: 701-5.
487. Orlic, D., Kajstura, J., Chimenti, S., et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A, 2001; 98: 10 344-9.
488. Jackson, K. A., Majka, S. M., Wang, H., et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest, 2001; 107: 1395-402.
489. Strauer, B. E., Brehm, M., Zeus, T., et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrowcell transplantationinhumans. Circulation, 2002;106: 1913-18.
490. Ferrari, G., Cusella-De Angelis, G., Coletta, M., et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 1998; 279: 1528-30.
491. Jackson, K. A., Mi, T., &Goodell, M. A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A, 1999; 96: 14482-6.
492. Petersen, B. E., Bowen, W. C., Patrene, K.D., et al. Bone marrow as a potential source of hepatic oval cells. Science, 1999; 284: 1168-70.
493. Lagasse, E., Connors, H., Al-Dhalimy, M., et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med, 2000; 6: 1229-34.
494. Theise, N.D., Badve, S., Saxena, R., et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology, 2000; 31: 235-40.
495. Theise, N. D., Nimmakayalu, M., Gardner, R., et al. Liver from bone marrow in humans. Hepatology, 2000; 32: 11-16.
496. Alison, M. R., Poulsom, R., Jeffery, R., et al. Hepatocytes from non-hepatic adult stem cells. Nature, 2000; 406: 257.
497. Krause, D. S., Theise, N. D., Collector, M. I., et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 2001; 105: 369-77.
498. Wang, X., Ge, S., McNamara, G., et al. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood, 2003; 101: 4201-8.
499. Ishikawa, F., Drake, C. J., Yang, S., et al. Transplanted human cordblood cells give rise to hepatocytes in engrafted mice. Ann N Y Acad Sci, 2003; 996: 174-85.
500. Eglitis, M. A.&Mezey, E. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A, 1997; 94: 4080-5.
501. Kopen, G. C., Prockop, D. J., & Phinney, D. G. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A, 2000; 96: 10711-16.
502. Brazelton, T. R., Rossi, F. M., Keshet, G. I., & Blau, H. M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science, 2000; 290: 1775-9.
503. Mezey, E., Chandross, K. J., Harta, G., Maki, R. A., &McKercher, S. R. Turning blood into brain: cells bearing neuronal antigens generated in vivo frombone marrow. Science, 2000; 290: 1779-82.
504. Wagers, A. J., Sherwood, R. I., Christensen, J. L., & Weissman, I. L. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science, 2002; 297: 2256-9.
505. Castro, R. F., Jackson, K. A., Goodell, M. A., et al. Failure of bonemarrowcells to transdifferentiate intoneural cells in vivo. Science, 2002; 297: 1299.
506. Wang, X., Willenbring, H., Akkari, Y., et al. Cell fusion istheprincipal source of bone-marrow-derived hepatocytes. Nature, 2003; 422: 897-901.
507. Balsam, L.B., Wagers, A. J., Christensen, J. L., et al. Haematopoieticstemcellsadoptmaturehaematopoieticfates inischaemic myocardium. Nature, 2004; 428: 668-73.
508. Murry, C. E., Soonpaa, M. H., Reinecke, H., et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 2004; 428: 664-8.
509. Taniguchi, H., Toyoshima, T., Fukao, K., & Nakauchi, H. Presence of hematopoietic stem cells in the adult liver. Nat Med, 1996; 2: 198-203.
510. Iwatani, H., Ito, T., Imai, E., et al. Hematopoietic and nonhematopoieticpotentials of Hoechst/sidepopulationcells isolated from adult rat kidney. Kidney Int, 2004; 65: 1604-14.
511. Ying, Q. L., Nichols, J., Evans, E. P., & Smith, A. G. Changing potency by spontaneous fusion. Nature, 2002; 416: 545-8.
512. Terada, N., Hamazaki, T., Oka, M., et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 2002; 416: 542-5.
513. Weimann, J. M., Johansson, C. B., Trejo, A., &Blau, H. M. Stable reprogrammedheterokaryonsformspontaneouslyin Purkinje neurons after bone marrow transplant. Nat Cell Biol, 2003; 5: 959-66.
514. Corbel, S. Y., Lee, A., Yi, L., et al. Contribution of hematopoietic stem cells to skeletal muscle. Nat Med, 2003; 9: 1528-32.
515. Camargo, F. D., Green, R., Capetenaki, Y., Jackson, K. A., & Goodell, M. A. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat Med, 2003; 9: 1520-7.
516. Van der Loo, J. C. M., Hanenberg, H., Cooper, R. J., et al. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse as a model system to study the engraftment and mobilization of human peripheral blood stem cells. Blood, 1998; 92: 2556-70.
517. Eaves, C., Cashman, J., & Eaves, A. Defective regulation of leukemic hematopoiesis in chronic myeloid leukemia. Leuk Res, 1998; 22: 1085-96.