Developmental changes in hematopoietic stem cell properties

Experimental and Molecular Medicine

Volumn 45, Issue 11, 2013, Pages

  Copley, Michael R ^a   Eaves, Connie J ^a,b  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Hematopoietic stem cells; HMGA2; Lin28 let7 pathway; Ontogeny; Self renewal

Indexed keywords

HIGH MOBILITY GROUP A2 PROTEIN; MICRORNA; RNA BINDING PROTEIN;

ANIMAL; CELL DIFFERENTIATION; CELL LINEAGE; CYTOLOGY; EMBRYONIC STEM CELL; GENETICS; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMIA; METABOLISM; REVIEW;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; EMBRYONIC STEM CELLS; HEMATOPOIETIC STEM CELLS; HMGA2 PROTEIN; HUMANS; LEUKEMIA; MICRORNAS; RNA-BINDING PROTEINS;

EID: 84892155757     PISSN: 12263613     EISSN: 20926413     Source Type: Journal    
DOI: 10.1038/emm.2013.98     Document Type: Review

References (122)

1. Szilvassy SJ, Ragland PL, Miller CL, Eaves CJ. The marrow homing efficiency of murine hematopoietic stem cells remains constant during ontogeny. Exp Hematol 2003; 31: 331-338.
2. Doulatov S, Notta F, Laurenti E, Dick JE. Hematopoiesis: A human perspective. Cell Stem Cell 2012; 10: 120-136.
3. Lessard J, Faubert A, Sauvageau G. Genetic programs regulating HSC specification, maintenance and expansion. Oncogene 2004; 23: 7199-7209.
4. Purton LE, Scadden DT. Limiting factors in murine hematopoietic stem cell assays. Cell Stem Cell 2007; 1: 263-270.
5. Dykstra B, Kent D, Bowie M, McCaffrey L, Hamilton M, Lyons K et al. Long-Term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell 2007; 1: 218-229.
6. Kent DG, Copley MR, Benz C, Wohrer S, Dykstra BJ, Ma E et al. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential. Blood 2009; 113: 6342-6350.
7. Benz C, Copley M, Kent D, Wohrer S, Cores A, Aghaeepour N et al. Hematopoietic stem cell subtypes expand differentially during development and display distinct lymphopoietic programs. Cell Stem Cell 2012; 10: 273-283.
8. Copley MR, Beer PA, Eaves CJ. Hematopoietic stem cell heterogeneity takes center stage. Cell Stem Cell 2012; 10: 690-697.
9. Becker AJ, McCulloch EA, Siminovitch L, Till JE. The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice. Blood 1965; 26: 296-308.
10. Schofield RA. Comparative study of repopulating potential of grafts from various haemopoietic sources: CFU repopulation. Cell Tissue Kinet 1970; 3: 119-130.
11. Micklem HS, Ford CE, Evans EP, Ogden DA, Papworth DS. Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice. J Cell Physiol 1972; 79: 293-298.
12. Signer RA, Morrison SJ. Mechanisms that regulate stem cell aging and life span. Cell Stem Cell 2013; 12: 152-165.
13. Till JE, McCulloch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 1961; 14: 213-222.
14. Siminovitch L, McCulloch EA, Till JE. The distribution of colony-forming cells among spleen colonies. J Cell Physiol 1963; 62: 327-336.
15. Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963; 197: 452-454.
16. Ploemacher RE, Brons RH. 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: 263-266.
17. Jones RJ, Collector MI, Barber JP, Vala MS, Fackler MJ, May WS et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood 1996; 88: 487-491.
18. Holyoake TL, Nicolini FE, Eaves CJ. Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrow. Exp Hematol 1999; 27: 1418-1427.
19. Nicolini FE, Holyoake TL, Cashman JD, Chu PP, Lambie K, Eaves CJ. Unique differentiation programs of human fetal liver stem cells shown both in vitro and in vivo in NOD/SCID mice. Blood 1999; 94: 2686-2695.
20. Cumano A, Godin I. Ontogeny of the hematopoietic system. Annu Rev Immunol 2007; 25: 745-785.
21. Palis J, Yoder MC. Yolk-sac hematopoiesis: The first blood cells of mouse and man. Exp Hematol 2001; 29: 927-936.
22. Wong PM, Chung SW, Eaves CJ, Chui DH. Ontogeny of the mouse hemopoietic system. Prog Clin Biol Res 1985; 193: 17-28.
23. Charbord P, Tavian M, Coulombel L, Luton D, San Clemente H, Humeau L et al. [Early ontogeny of the human hematopoietic system]. C R Seances Soc Biol Fil 1995; 189: 601-609.
24. Medvinsky AL, Samoylina NL, Muller AM, Dzierzak EA. An early pre-liver intraembryonic source of CFU-S in the developing mouse. Nature 1993; 364: 64-67.
25. Muller AM, Medvinsky A, Strouboulis J, Grosveld F, Dzierzak E. Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1994; 1: 291-301.
26. Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996; 86: 897-906.
27. de Bruijn MF, Speck NA, Peeters MC, Dzierzak E. Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. EMBO J 2000; 19: 2465-2474.
28. Ivanovs A, Rybtsov S, Welch L, Anderson RA, Turner ML, Medvinsky A. Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region. J Exp Med 2011; 208: 2417-2427.
29. Gekas C, Dieterlen-Lievre F, Orkin SH, Mikkola HK. The placenta is a niche for hematopoietic stem cells. Dev Cell 2005; 8: 365-375.
30. Rhodes KE, Gekas C, Wang Y, Lux CT, Francis CS, Chan DN et al. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell 2008; 2: 252-263.
31. Van Handel B, Prashad SL, Hassanzadeh-Kiabi N, Huang A, Magnusson M, Atanassova B et al. The first trimester human placenta is a site for terminal maturation of primitive erythroid cells. Blood 2010; 116: 3321-3330.
32. Kumaravelu P, Hook L, Morrison AM, Ure J, Zhao S, Zuyev S et al. Quantitative developmental anatomy of definitive haematopoietic stem cells/long-Term repopulating units (HSC/RUs): Role of the aorta-gonadmesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver. Development 2002; 129: 4891-4899.
33. Yoder MC, Hiatt K, Mukherjee P. In vivo repopulating hematopoietic stem cells are present in the murine yolk sac at day 9.0 postcoitus. Proc Natl Acad Sci USA 1997; 94: 6776-6780.
34. Houssaint E. Differentiation of the mouse hepatic primordium. II. Extrinsic origin of the haemopoietic cell line. Cell Differ 1981; 10: 243-252.
35. Johnson GR, Moore MA. Role of stem cell migration in initiation of mouse foetal liver haemopoiesis. Nature 1975; 258: 726-728.
36. Fleischman RA, Custer RP, Mintz B. Totipotent hematopoietic stem cells: Normal self-renewal and differentiation after transplantation between mouse fetuses. Cell 1982; 30: 351-359.
37. Yoder MC. Generation of HSCs in the embryo and assays to detect them. Oncogene 2004; 23: 7161-7163.
38. Mikkola HK, Orkin SH. The journey of developing hematopoietic stem cells. Development 2006; 133: 3733-3744.
39. Robb L, Lyons I, Li R, Hartley L, Kontgen F, Harvey RP et al. Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc Natl Acad Sci USA 1995; 92: 7075-7079.
40. Shivdasani RA, Mayer EL, Orkin SH. Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature 1995; 373: 432-434.
41. Samokhvalov IM, Samokhvalova NI, Nishikawa S. Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 2007; 446: 1056-1061.
42. McGrath K, Palis J. Ontogeny of erythropoiesis in the mammalian embryo. Curr Top Dev Biol 2008; 82: 1-22.
43. Rich IN, Kubanek B. Erythroid colony formation (Cfue) in fetal liver and adult bone-marrow and spleen from mouse. Blut 1976; 33: 171-180.
44. Rich IN, Kubanek B. The ontogeny of erythropoiesis in the mouse detected by the erythroid colony-forming technique.2. Transition in erythropoietin sensitivity during development. J Embryol Exp Morph 1980; 58: 143-155.
45. DeAlarcon PA, Graeve JLA. Analysis of megakaryocyte ploidy in fetal bone marrow biopsies using a new adaptation of the feulgen technique to measure DNA content and estimate megakaryocyte ploidy from biopsy specimens. Pediatr Res 1996; 39: 166-170.
46. Graeve JLA, Dealarcon PA. Megakaryocytopoiesis in the human-fetus. Arch Dis Child 1989; 64: 481-484.
47. Ma DC, Sun YH, Chang KZ, Zuo W. Developmental change of megakaryocyte maturation and DNA ploidy in human fetus. Eur J Haematol 1996; 57: 121-127.
48. Liu ZJ, Italiano J, Ferrer-Marin F, Gutti R, Bailey M, Poterjoy B et al. Developmental differences in megakaryocytopoiesis are associated with up-regulated TPO signaling through mTOR and elevated GATA-1 levels in neonatal megakaryocytes. Blood 2011; 117: 4106-4117.
49. Murray NA, Watts TL, Roberts IAG. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res 1998; 43: 148-151.
50. Nishihira H, Toyoda Y, Miyazaki H, Kigasawa H, Ohsaki E. Growth of macroscopic human megakaryocyte colonies from cord blood in culture with recombinant human thrombopoietin (c-mpl ligand) and the effects of gestational age on frequency of colonies. Br J Haematol 1996; 92: 23-28.
51. Klimchenko O, Di Stefano A, Geoerger B, Hamidi S, Opolon P, Robert T et al. Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions. Blood 2011; 117: 3065-3075.
52. Hayakawa K, Hardy RR, Herzenberg LA, Herzenberg LA. Progenitors for Ly-1 B-Cells are distinct from progenitors for other B-cells. J Exp Med 1985; 161: 1554-1568.
53. Carvalho TL, Mota-Santos T, Cumano A, Demengeot J, Vieira P. Arrested B lymphopoiesis and persistence of activated B cells in adult interleukin 7(-/-) mice. J Exp Med 2001; 194: 1141-1150.
54. Carey JB, Moffatt-Blue CS, Watson LC, Gavin AL, Feeney AJ. Repertoirebased selection into the marginal zone compartment during B cell development. J Exp Med 2008; 205: 2043-2052.
55. Yoshimoto M, Montecino-Rodriguez E, Ferkowicz MJ, Porayette P, Shelley WC, Conway SJ et al. Embryonic day 9 yolk sac and intraembryonic hemogenic endothelium independently generate a B-1 and marginal zone progenitor lacking B-2 potential. Proc Natl Acad Sci USA 2011; 108: 1468-1473.
56. Havran WL, Allison JP. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 1988; 335: 443-445.
57. Ikuta K, Kina T, MacNeil I, Uchida N, Peault B, Chien YH et al. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 1990; 62: 863-874.
58. Benlagha K, Kyin T, Beavis A, Teyton L, Bendelac A. A thymic precursor to the NK T cell lineage. Science 2002; 296: 553-555.
59. Gapin L, Matsuda JL, Surh CD, Kronenberg M. NKT cells derive from double-positive thymocytes that are positively selected by CD1d. Nat Immunol 2001; 2: 971-978.
60. Yuan J, Nguyen CK, Liu X, Kanellopoulou C, Muljo SA. Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis. Science 2012; 335: 1195-1200.
61. Challen GA, Boles NC, Chambers SM, Goodell MA. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1. Cell Stem Cell 2010; 6: 265-278.
62. Morita Y, Ema H, Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med 2010; 207: 1173-1182.
63. Heyworth C, Pearson S, May G, Enver T. Transcription factor-mediated lineage switching reveals plasticity in primary committed progenitor cells. EMBO J 2002; 21: 3770-3781.
64. Sieburg HB, Cho RH, Dykstra B, Uchida N, Eaves CJ, Muller-Sieburg CE. The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets. Blood 2006; 107: 2311-2316.
65. Bowie MB, Kent DG, Dykstra B, McKnight KD, McCaffrey L, Hoodless PA et al. Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties. Proc Natl Acad Sci USA 2007; 104: 5878-5882.
66. Fleming WH, Alpern EJ, Uchida N, Ikuta K, Spangrude GJ, Weissman IL. Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. J Cell Biol 1993; 122: 897-902.
67. Morrison SJ, Hemmati HD, Wandycz AM, Weissman IL. The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci USA 1995; 92: 10302-10306.
68. Bowie MB, McKnight KD, Kent DG, McCaffrey L, Hoodless PA, Eaves CJ. Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect. J Clin Invest 2006; 116: 2808-2816.
69. Rufer N, Brummendorf TH, Kolvraa S, Bischoff C, Christensen K, Wadsworth L 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 ExpMed 1999; 190: 157-167.
70. Sidorov I, Kimura M, Yashin A, Aviv A. Leukocyte telomere dynamics and human hematopoietic stem cell kinetics during somatic growth. Exp Hematol 2009; 37: 514-524.
71. Baerlocher GM, Rice K, Vulto I, Lansdorp PM. Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age. Aging cell 2007; 6: 121-123.
72. Ye M, Zhang H, Amabile G, Yang H, Staber PB, Zhang P et al. C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nat Cell Biol 2013; 15: 385-394.
73. Trumpp A, Essers M, Wilson A. Awakening dormant haematopoietic stem cells. Nat Rev Immunol 2010; 10: 201-209.
74. Venezia TA, Merchant AA, Ramos CA, Whitehouse NL, Young AS, Shaw CA et al. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol 2004; 2: 1640-1651.
75. McKinney-Freeman S, Cahan P, Li H, Lacadie SA, Huang HT, Curran M et al. The transcriptional landscape of hematopoietic stem cell ontogeny. Cell Stem Cell 2012; 11: 701-714.
76. Rebel VI, Miller CL, Thornbury GR, Dragowska WH, Eaves CJ, Lansdorp PM. A comparison of long-Term repopulating hematopoietic stem cells in fetal liver and adult bone marrow from the mouse. Exp Hematol 1996; 24: 638-648.
77. Rebel VI, Miller CL, Eaves CJ, Lansdorp PM. The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts. Blood 1996; 87: 3500-3507.
78. Pawliuk R, Eaves C, Humphries RK. Evidence of both ontogeny and transplant dose-regulated expansion of hematopoietic stem cells in vivo. Blood 1996; 88: 2852-2858.
79. McCulloch EA, Siminovitch L, Till JE. Spleen-colony formation in anemic mice of genotype Ww. Science 1964; 144: 844-846.
80. Geissler EN, Mcfarland EC, Russell ES. Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse-A description of 10 new W-Alleles. Genetics 1981; 97: 337-361.
81. Miller CL, Rebel VI, Lemieux ME, Helgason CD, Lansdorp PM, Eaves CJ. Studies of W mutant mice provide evidence for alternate mechanisms capable of activating hematopoietic stem cells. Exp Hematol 1996; 24: 185-194.
82. Huang E, Nocka K, Beier DR, Chu TY, Buck J, Lahm HW et al. The hematopoietic growth factor-Kl is encoded by the Si-locus and is the ligand of the C-Kit receptor, the gene-product of the W-locus. Cell 1990; 63: 225-233.
83. Ikuta K, Weissman IL. Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proc Natl Acad Sci USA 1992; 89: 1502-1506.
84. Bowie MB, Kent DG, Copley MR, Eaves CJ. Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells. Blood 2007; 109: 5043-5048.
85. Ashman LK. The biology of stem cell factor and its receptor C-kit. Int J Biochem Cell B. 1999; 31: 1037-1051.
86. Audet J, Miller CL, Eaves CJ, Piret JM. Common and distinct features of cytokine effects on hematopoietic stem and progenitor cells revealed by dose-response surface analysis. Biotechnol Bioeng 2002; 80: 393-404.
87. Zandstra PW, Conneally E, Petzer AL, Piret JM, Eaves CJ. Cytokine manipulation of primitive human hematopoietic cell self-renewal. Proc Natl Acad Sci USA 1997; 94: 4698-4703.
88. Uchida N, Dykstra B, Lyons KJ, Leung FY, Eaves CJ. Different in vivo repopulating activities of purified hematopoietic stem cells before and after being stimulated to divide in vitro with the same kinetics. Exp Hematol 2003; 31: 1338-1347.
89. Kikuchi K, Kondo M. Developmental switch of mouse hematopoietic stem cells from fetal to adult type occurs in bone marrow after birth. Proc Natl Acad Sci USA 2006; 103: 17852-17857.
90. Kiel MJ, Iwashita T, Yilmaz OH, Morrison SJ. Spatial differences in hematopoiesis but not in stem cells indicate a lack of regional patterning in definitive hematopoietic stem cells. Dev Biol 2005; 283: 29-39.
91. Copley MR, Babovic S, Benz C, Knapp DJ, Beer PA, Kent DG et al. The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells. Nat Cell Biol 2013; 15: 916-925.
92. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423: 302-305.
93. Hock H, Hamblen MJ, Rooke HM, Schindler JW, Saleque S, Fujiwara Y et al. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 2004; 431: 1002-1007.
94. Hock H, Meade E, Medeiros S, Schindler JW, Valk PJ, Fujiwara Y et al. Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev 2004; 18: 2336-2341.
95. Kim I, Saunders TL, Morrison SJ. Sox17 dependence distinguishes the transcriptional regulation of fetal from adult hematopoietic stem cells. Cell 2007; 130: 470-483.
96. He S, Kim I, Lim MS, Morrison SJ. Sox17 expression confers self-renewal potential and fetal stem cell characteristics upon adult hematopoietic progenitors. Genes Dev 2011; 25: 1613-1627.
97. Zhang CC, Lodish HF. Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells. Blood 2004; 103: 2513-2521.
98. Zhang CC, Kaba M, Ge G, Xie K, Tong W, Hug C et al. Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells. Nat Med 2006; 12: 240-245.
99. Gutti RK, Sallmon H, Liu ZJ, Ferrer-Marin F, Cantor A, Bailey M et al. Developmental differences in the Let-7b/IMP-1/IGF-II axis contribute to the high proliferative rate of neonatal megakaryocyte progenitors. Blood 2010; 116: 674.
100. Lee YT, de Vasconcellos JF, Yuan J, Byrnes C, Noh SJ, Meier ER et al. LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Blood 2013; 122: 1034-1041.
101. Bussing I, Slack FJ, Grosshans H. let-7 microRNAs in development, stem cells and cancer. Trends Mol Med 2008; 14: 400-409.
102. Scotting PJ, Walker DA, Perilongo G. Childhood solid tumours: A developmental disorder. Nat Rev Cancer. 2005; 5: 481-488.
103. Roberts KG, Mullighan CG. How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia. Curr Opin Pediatr 2011; 23: 34-40.
104. Speck NA, Gilliland DG. Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer 2002; 2: 502-513.
105. Schindler JW, Van Buren D, Foudi A, Krejci O, Qin J, Orkin SH et al. TEL-AML1 corrupts hematopoietic stem cells to persist in the bone marrow and initiate leukemia. Cell Stem Cell 2009; 5: 43-53.
106. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME et al. Noonan syndrome: Clinical features, diagnosis, and management guidelines. Pediatrics 2010; 126: 746-759.
107. Matsuda K, Shimada A, Yoshida N, Ogawa A, Watanabe A, Yajima S et al. Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. Blood 2007; 109: 5477-5480.
108. Gamis AS, Smith FO. Transient myeloproliferative disorder in children with Down syndrome: Clarity to this enigmatic disorder. Br J Haematol 2012; 159: 277-287.
109. Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S et al. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 2009; 41: 843-U109.
110. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer 2007; 7: 899-910.
111. Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME. The role of let-7 in cell differentiation and cancer. Endocr-Relat cancer 2010; 17: F19-F36.
112. Li Z, Zhang Y, Ramanujan K, Ma Y, Kirsch DG, Glass DJ. Oncogenic NRAS, required for pathogenesis of embryonic rhabdomyosarcoma, relies upon the HMGA2-IGF2BP2 pathway. Cancer Res 2013; 73: 3041-3050.
113. Copelan EA. Hematopoietic stem-cell transplantation. New Engl J Med 2006; 354: 1813-1826.
114. Takizawa H, Schanz U, Manz MG. Ex vivo expansion of hematopoietic stem cells: Mission accomplished? Swiss Med Wkly 2011; 141: W13316.
115. Kardel MD, Eaves CJ. Modeling human hematopoietic cell development from pluripotent stem cells. Exp Hematol 2012; 40: 601-611.
116. Broxmeyer HE, Cooper S, Hass DM, Hathaway JK, Stehman FB, Hangoc G. Experimental basis of cord blood transplantation. Bone Marrow Transplant 2009; 44: 627-633.
117. Wang GP, Berry CC, Malani N, Leboulch P, Fischer A, Hacein-Bey-Abina S et al. Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial. Blood 2010; 115: 4356-4366.
118. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-Thalassaemia. Nature 2010; 467: 318-322.
119. Li Z, Gilbert JA, Zhang Y, Zhang M, Qiu Q, Ramanujan K et al. An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis. Dev Cell 2012; 23: 1176-1188.
120. Nishino J, Kim I, Chada K, Morrison SJ. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell 2008; 135: 227-239.
121. Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T, Morrison SJ. Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 2002; 35: 657-669.
122. Toledano H, D'Alterio C, Czech B, Levine E, Jones DL. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature 2012; 485: 605-610.