Uncertainty in the niches that maintain haematopoietic stem cells

Nature Reviews Immunology

Volumn 8, Issue 4, 2008, Pages 290-301

  Kiel, Mark J ^a   Morrison, Sean J ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN; CATHEPSIN K; GELATINASE B; JAGGED1; NERVE CELL ADHESION MOLECULE; OSTEOPONTIN; STEM CELL ANTIGEN 1; STROMAL CELL DERIVED FACTOR 1; THROMBOPOIETIN;

BONE MARROW CELL; CELL DIFFERENTIATION; CELL MIGRATION; HEMATOPOIETIC STEM CELL; HUMAN; NONHUMAN; OSTEOBLAST; OSTEOCLAST; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; REVIEW;

ANIMALS; BLOOD VESSELS; BONE AND BONES; BONE MARROW; BONE MARROW CELLS; CELL DIFFERENTIATION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELLS; HUMANS; OSTEOBLASTS; OSTEOCLASTS; SPLEEN;

EID: 41149109622     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri2279     Document Type: Review

References (108)

1. Molofsky, A. V., Pardal, R. & Morrison, S. J. Diverse mechanisms regulate stem cell self-renewal. Curr. Opin. in Cell Biol. 16, 700-707 (2004).
2. Adams, G. B. & Scadden, D. T. The hematopoietic stem cell in its place. Nature Immunology 7, 333-337 (2006).
3. Schofield, R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4, 7-25 (1978).
4. Suda, T., Arai, F. & Hirao, A. Hematopoietic stem cells and their niche. Trends Immunol. 26, 426-433 (2005).
5. Li, L. & Xie, T. Stem cell niche: structure and function. Annu. Rev. Cell Dev. Biol. 21, 605-631 (2005).
6. Kiel, M. J., Yilmaz, O. H., Iwashita, T., Terhorst, C. & Morrison, S. J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121, 1109-1121 (2005). In this study, HSCs were highly purified using simple combinations of SLAM family markers, making it possible to localize HSCs in tissue sections. Many HSCs localized to sinusoids in bone marrow and spleen, raising the possibility of perivascular niches.
7. Kiel, M. J., Radice, G. L. & Morrison, S. J. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cell 1, 204-217 (2007).
8. Sugiyama, T., Kohara, H., Noda, M. & Nagasawa, T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977-988 (2006). This paper reports that reticular cells adjacent to HSCs in both perivascular and endosteal sites are a major source of CXCL12 (a factor required for HSC maintenance) suggesting that these reticular cells are an important component of HSC niches.
9. Sacchetti, B. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131, 324-336 (2007). Perivascular mesenchymal progenitors were found to re-establish HSC niches after transplantation, and to secrete factors that regulate HSC maintenance (such as angiopoietin) into the perivascular environment.
10. Franz-Odendaal, T. A., Hall, B. K. & Witten, P. E. Buried alive: how osteoblasts become osteocytes. Dev. Dyn. 235, 176-190 (2006).
11. Seeman, E. & Delmas, P. D. Bone quality - the material and structural basis of bone strength and fragility. N. Engl. J. Med. 354, 2250-2261 (2006).
12. De Bruyn, P. P., Breen, P. C. & Thomas, T. B. The microcirculation of the bone marrow. Anat. Rec. 168, 55-68 (1970).
13. Morrison, S. J. & Weissman, I. L. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1, 661-673 (1994).
14. Spangrude, G. J., Brooks, D. M. & Tumas, D. B. Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function. Blood 85, 1006-1016 (1995).
15. 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-rhodamine 123 FACS selection. Exp. Hematol. 21, 614-622 (1993).
16. Lord, B. I., Testa, N. G. & Hendry, J. H. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood 46, 65-72 (1975).
17. Gong, J. K. Endosteal marrow: a rich source of hematopoietic stem cells. Science 199, 1443-1445 (1978).
18. Maloney, M. A., Lamela, R. A., Dorie, M. J. & Patt, H. M. Concentration gradient of blood stem cells in mouse bone marrow - an open question. Blood 51, 521-525 (1978).
19. Calvi, L. M. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425, 841-846 (2003). This paper demonstrated an increase in the frequency of HSCs in bone marrow when constitutively active parathyroid hormone receptor was over-expressed in osteoblasts or when parathyroid hormone was exogenously administered to irradiated mice, suggesting that osteoblasts are capable of regulating HSC numbers in bone marrow.
20. Zhang, J. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836-841 (2003). This study shows that the conditional inactivation of the bone morphogenetic protein receptor type IA leads to an increase in osteoblasts, trabecular bone and HSCs, demonstrating that osteoblasts or trabecular bone can regulate HSC numbers in the bone marrow.
21. Arai, F. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161 (2004). This paper suggests that angiopoietin is an important element of the HSC niche that promotes HSC maintenance by promoting quiescence.
22. Stier, S. et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J. Exp. Med. 201, 1781-1791 (2005).
23. Nilsson, S. K. et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106, 1232-1239 (2005).
24. Nilsson, S. K., Johnston, H. M. & Coverdale, J. A. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood 97, 2293-2299 (2001).
25. Suzuki, N. et al. Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche. Proc. Natl Acad. Sci. USA 103, 2202-2207 (2006).
26. Yoshihara, H. et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with in the osteoblastic niche. Cell Stem Cell 1, 685-697 (2007).
27. Petit, I. et al. G.-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nature Immunol. 3, 687-694 (2002).
28. Qian, H. et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell 1, 671-684 (2007).
29. Peled, A. et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283, 845-848 (1999).
30. Puri, M. C. & Bernstein, A. Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis. Proc. Natl Acad. Sci. USA 100, 12753-12758 (2003).
31. Kaushansky, K. Thrombopoietin: accumulating evidence for an important biological effect on the hematopoietic stem cell. Ann. N. Y Acad. Sci. 996, 39-43 (2003).
32. Solar, G. P. et al. Role of c-mpl in early hematopoiesi. Blood 92, 4-10 (1998).
33. Kimura, S., Roberts, A. W., Metcalf, D. & Alexander, W. S. Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin. Proc. Natl Acad. Sci. USA 95, 1195-1200 (1998).
34. Li, J. J., Huang, Y. Q., Basch, R. & Karpatkin, S. Thrombin induces the release of angiopoietin-1 from platelets. Thromb. Haemost. 85, 204-206 (2001).
35. Guerriero, A. et al. Thrombopoietin is synthesized by bone marrow stromal cells. Blood 90, 3444-3455 (1997).
36. Sungaran, R., Markovic, B. & Chong, B. H. Localization and regulation of thrombopoietin mRNA expression in human kidney, liver, bone marrow, and spleen using in situ hybridization. Blood 89, 101-107 (1997).
37. Wilson, A. et al. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. 18, 2747-2763 (2004).
38. Kiel, M. J. et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449, 238-242 (2007).
39. Mancini, S. J. et al. Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. Blood 105, 2340-2342 (2005).
40. Taichman, R. S. & Emerson, S. G. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J. Exp. Med. 179, 1677-1682 (1994).
41. Visnjic, D. et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103, 3258-3264 (2004).
42. + cells (which are enriched for HSCs).
43. Kollet, O. et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Med. 12, 657-664 (2006). This paper demonstrated that receptor activated by nuclear factor-κB ligand (RANKL) stimulation of osteoclasts promoted the mobilization of haematopoietic progenitors into circulation in a CXCL12-dependent manner, suggesting that osteoclasts contribute to the regulation of the endosteal niche.
44. Adams, G. B. et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439, 599-603 (2006). This paper demonstrated reduced cellularity and HSC content of postnatal bone marrow and increased progenitor mobilization in calcium-sensing-receptor-deficient mice suggesting that HSC localization to the bone marrow is regulated by calcium concentration.
45. Zou, Y. R., Kottmann, A. H., Kuroda, M., Taniuchi, I. & Littman, D. R. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393, 595-599 (1998).
46. Ara, T. et al. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 19, 257-267 (2003).
47. Heissig, B. et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109, 625-637 (2002).
48. Nilsson, S. K., Johnston, H. M. & Coverdale, J. A. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood 97, 2293-2299 (2001).
49. Murayama, E. et al. Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. Immunity 25, 963-975 (2006).
50. Zon, L. I. Developmental biology of hematopoiesis. Blood 86, 2876-2891 (1995).
51. Huber, T. L., Kouskoff, V., Fehling, H. J., Palis, J. & Keller, G. Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature 432, 625-630 (2004).
52. Kennedy, M. et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 386, 488-493 (1997).
53. Mikkola, H. K. & Orkin, S. H. The journey of developing hematopoietic stem cells. Development 133, 3733-3744 (2006).
54. de Bruijn, M. F. et al. Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta. Immunity 16, 673-683 (2002).
55. 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 5, 513-525 (1996).
56. Cumano, A., Dieterlen-Lievre, F. & Godin, I. Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 86, 907-916 (1996).
57. North, T. E. et al. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16, 661-672 (2002).
58. Medvinsky, A. & Dzierzak, E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86, 897-906 (1996).
59. Gekas, C., Dieterlen-Lievre, F., Orkin, S. H. & Mikkola, H. K. The placenta is a niche for hematopoietic stem cells. Dev. Cell 8, 365-375 (2005).
60. Ottersbach, K. & Dzierzak, E. The murine placenta contains hematopoietic stem cells within the vascular labyrinth region. Dev. Cell 8, 377-387 (2005).
61. Taniguchi, H., Toyoshima, T., Fukao, K. & Nakauchi, H. Presence of hematopoietic stem cells in the adult liver. Nature Medicine 2, 198-203 (1996).
62. Johnson, R. S., Spiegelman, B. M. & Papaioannou, V. Pleiotropic effects of a null mutation in the c-fos proto-oncogene. Cell 71, 577-586 (1992).
63. 0-thalassemia. Proc. Natl Acad. Sci. USA 92, 11608-11612 (1995).
64. Laterveer, L., Lindley, I. J., Hamilton, M. S., Willemze, R. & Fibbe, W. E. Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood 85, 2269-2275 (1995).
65. Gu, Y. et al. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302, 445-449 (2003).
66. Cancelas, J. A. et al. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nature Med. 11, 886-891 (2005).
67. Kopp, H. G., Avecilla, S. T., Hooper, A. T. & Rafii, S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda) 20, 349-356 (2005).
68. Wright, D. E., Wagers, A. J., Gulati, A. P., Johnson, F. L. & Weissman, I. L. Physiological migration of hematopoietic stem and progenitor cells. Science 294, 1933-1936 (2001).
69. Li, W., Johnson, S. A., Shelley, W. C. & Yoder, M. C. Hematopoietic stem cell repopulating ability can be maintained in vitro by some primary endothelial cells. Exp. Hematol. 32, 1226-1237 (2004).
70. Ohneda, O. et al. Hematopoietic stem cell maintenance and differentiation are supported by embryonic aorta-gonad-mesonephros region-derived endothelium. Blood 92, 908-919 (1998).
71. Yao, L., Yokota, T., Xia, L., Kincade, P. W. & McEver, R. P. Bone marrow dysfunction in mice lacking the cytokine receptor gp130 in endothelial cells. Blood 106, 4093-4101 (2005). This study shows that conditional loss of GP130 in endothelial cells leads to a reduction in bone-marrow cellularity, particularly around sinusoids, demonstrating that endothelial-cell function is required for maintaining haematopoiesis in vivo.
72. Koni, P. A. et al. Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J. Exp. Med. 193, 741-754 (2001).
73. Dar, A. et al. Chemokine receptor CXCR4-dependent internalization and resecretion of functional chemokine SDF-1 by bone marrow endothelial and stromal cells. Nature Immunol. 6, 1038-1046 (2005).
74. Shi, S. & Gronthos, S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J. Bone Miner. Res. 18, 696-704 (2003).
75. Kaigler, D. et al. Endothelial cell modulation of bone marrow stromal cell osteogenic potential. FASEB J. 19, 665-667 (2005).
76. Avecilla, S. T. et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Med. 10, 64-71 (2004).
77. low mice). Blood 100, 1123-1132 (2002).
78. Shivdasani, R. A. & Orkin, S. H. Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. Proc. Natl Acad. Sci. USA 92, 8690-8694 (1995).
79. Kacena, M. A., Gundberg, C. M. & Horowitz, M. C. A reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells. Bone 39, 978-984 (2006).
80. Sipkins, D. A. et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 435, 969-973 (2005).
81. DiMascio, L. et al. Identification of adiponectin as a novel hemopoietic stem cell growth factor. J. Immunol. 178, 3511-3520 (2007).
82. Durand, R. E., Chaplin, D. J. & Olive, P. L. Cell sorting with Hoechst or carbocyanine dyes as perfusion probes in spheroids and tumors. Methods Cell Biol. 33, 509-518 (1990).
83. Parmar, K., Mauch, P., Vergilio, J. A., Sackstein, R. & Down, J. D. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc. Natl Acad. Sci. USA 104, 5431-5436 (2007).
84. Levesque, J. P. et al. Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxia-inducible transcription factor-1α and vascular endothelial growth factor A in bone marrow. Stem Cells 25, 1954-1965 (2007).
85. Katayama, Y. et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124, 407-421 (2006). This study shows that mutations or drug treatments that reduce the function of the sympathetic nervous system also reduce progenitor mobilization from the bone marrow, indicating that the migration and localization of haematopoietic progenitors are regulated by the nervous system.
86. Julien, C., Zhang, Z. Q. & Barres, C. How sympathetic tone maintains or alters arterial pressure. Fundam Clin. Pharmacol. 9, 343-349 (1995).
87. Fuller, M. T. & Spradling, A. C. Male and female Drosophila germline stem cells: two versions of immortality. Science 316, 402-404 (2007).
88. Varnum-Finney, B. et al. The notch ligand, jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 91, 4084-4091 (1998).
89. Stier, S., Cheng, T., Dombkowski, D., Carlesso, N. & Scadden, D. T. Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood 99, 2369-2378 (2002).
90. Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409-414 (2003).
91. Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 423, 448-452 (2003).
92. Scheller, M. et al. Hematopoietic stem cell and multilineage defects generated by constitutive β-catenin activation. Nature Immunol. 7, 1037-1047 (2006).
93. Kirstetter, P., Anderson, K., Porse, B. T., Jacobsen, S. E. & Nerlov, C. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nature Immunol. 7, 1048-1056 (2006).
94. Cobas, M. et al. β-catenin is dispensable for hematopoiesis and lymphopoiesis. J. Exp. Med. 199, 221-229 (2004).
95. 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. USA 92, 10302-10306 (1995).
96. Bodine, D. M., Seidel, N. E., Zsebo, K. M. & Orlic, D. In vivo administration of stem cell factor to mice increases the absolute number of pluripotent hematopoietic stem cells. Blood 82, 445-455 (1993).
97. Morrison, S. J., Wright, D. & Weissman, I. L. Cyclophosphamide/ granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization. Proc. Natl Acad. Sci. USA 94, 1908-1913 (1997).
98. Tulina, N. & Matunis, E. Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling. Science 294, 2546-2549 (2001).
99. Kiger, A. A., Jones, D. L., Schulz, C., Rogers, M. B. & Fuller, M. T. Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue. Science 294, 2542-2545 (2001).
100. Morrison, S. J. & Kimble, J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 441, 1068-1074 (2006).
101. Brawley, C. & Matunis, E. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science 304, 1331-1334 (2004).
102. Street, J. et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Natl Acad. Sci. USA 99, 9656-9661 (2002).
103. Tombran-Tink, J. & Barnstable, C. J. Osteoblasts and osteoclasts express PEDF, VEGF-A isoforms, and VEGF receptors: possible mediators of angiogenesis and matrix remodeling in the bone. Biochem. Biophys. Res. Commun. 316, 573-579 (2004).
104. Kiel, M. J. & Morrison, S. J. Maintaining hematopoietic stem cells in the vascular niche. Immunity 25, 862-864 (2006).
105. Nagasawa, T. et al. Defects of B-cell lymphopoiesis and bone marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, 635-638 (1996).
106. Trowbridge, J. J., Scott, M. P. & Bhatia, M. Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic regeneration. Proc. Natl Acad. Sci. USA 103, 14134-14139 (2006).
107. Barker, J. E. Sl/Sld hematopoietic progenitors are deficient in situ. Exp. Hematol. 22, 174-177 (1994).
108. McCarthy, K. F., Ledney, G. D. & Mitchell, R. A deficiency of hematopoietic stem cells in steel mice. Cell Tissue Kinet. 10, 121-126 (1977).