Bone-marrow haematopoietic-stem-cell niches (original) (raw)

• Fuchs, E., Tumbar, T. & Guasch, G. Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778 (2004).
  Article CAS PubMed Google Scholar
• Osawa, M., Hanada, K., Hamada, H. & Nakauchi, H. Long-term lymphohematopoietic reconstitution by a single CD34−low/negative hematopoietic stem cell. Science 273, 242–245 (1996).
  Article CAS PubMed Google Scholar
• Watt, F. M. & Hogan, B. L. Out of Eden: stem cells and their niches. Science 287, 1427–1430 (2000).
  Article CAS PubMed Google Scholar
• Weissman, I. L. Stem cells: units of development, units of regeneration, and units in evolution. Cell 100, 157–168 (2000).
  Article CAS PubMed Google Scholar
• Kondo, M. et al. Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu. Rev. Immunol. 21, 759–806 (2003).
  Article CAS PubMed Google Scholar
• Till, J. E. & McCulloch, C. E. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 14, 213–222 (1961).
  Article CAS PubMed Google Scholar
• Wagers, A. J., Sherwood, R. I., Christensen, J. L. & Weissman, I. L. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256–2259 (2002).
  Article CAS PubMed Google Scholar
• Matsuzaki, Y., Kinjo, K., Mulligan, R. C. & Okano, H. Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity 20, 87–93 (2004).
  Article CAS PubMed Google Scholar
• 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). This study shows that CD150, one of the signalling lymphocytic activation molecules (SLAMs) is expressed by LTR HSCs. CD150+ HSCs were localized near sinusoids in normal bone marrow, indicating that in addition to the endosteal niche a second vascular niche might exist.
  Article CAS PubMed Google Scholar
• Curry, J. L., Trentin, J. J. & Wolf, N. Hemopoietic spleen colony studies. II. Erythropoiesis. J. Exp. Med. 125, 703–720 (1967).
  Article CAS PubMed PubMed Central Google Scholar
• Schofield, R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4, 7–25 (1978). This paper proposes that HSCs are associated with other cell types, and that these allow self-renewal but prevent cell maturation. Schofield termed this microenvironment the 'stem-cell niche'
  CAS PubMed Google Scholar
• McCulloch, E. A., Siminovitch, L., Till, J. E., Russell, E. S. & Bernstein, S. E. The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sl d. Blood 26, 399–410 (1965). This paper (together with references 13 and 14) shows that normal bone marrow fails to engraft in Sl/Sl d mice. This is probably the first study demonstrating that the microenvironment is essential for bone-marrow HSC function and/or maintenance.
  CAS PubMed Google Scholar
• Barker, J. E. Sl/Sld hematopoietic progenitors are deficient in situ. Exp. Hematol. 22, 174–177 (1994).
  CAS PubMed Google Scholar
• Barker, J. E. Early transplantation to a normal microenvironment prevents the development of Steel hematopoietic stem cell defects. Exp. Hematol. 25, 542–547 (1997).
  CAS PubMed Google Scholar
• Nilsson, S. K. & Simmons, P. J. Transplantable stem cells: home to specific niches. Curr. Opin. Hematol. 11, 102–106 (2004).
  Article PubMed Google Scholar
• Ohlstein, B., Kai, T., Decotto, E. & Spradling, A. The stem cell niche: theme and variations. Curr. Opin. Cell Biol. 16, 693–699 (2004).
  Article CAS PubMed Google Scholar
• Spradling, A., Drummond-Barbosa, D. & Kai, T. Stem cells find their niche. Nature 414, 98–104 (2001).
  Article CAS PubMed Google Scholar
• Wu, A. M., Siminovitch, L., Till, J. E. & McCulloch, E. A. Evidence for a relationship between mouse hemopoietic stem cells and cells forming colonies in culture. Proc. Natl Acad. Sci. USA 59, 1209–1215 (1968).
  Article CAS PubMed PubMed Central Google Scholar
• Domen, J. & Weissman, I. L. Self-renewal, differentiation or death: regulation and manipulation of hematopoietic stem cell fate. Mol. Med. Today 5, 201–208 (1999).
  Article CAS PubMed Google Scholar
• Yang, L. et al. Identification of Lin−Sca1+kit+CD34+Flt3− short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 105, 2717–2723 (2005).
  Article CAS PubMed Google Scholar
• Adolfsson, J. et al. Identification of Flt3+lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121, 295–306 (2005).
  Article CAS PubMed Google Scholar
• Christensen, J. L. & Weissman, I. L. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc. Natl Acad. Sci. USA 98, 14541–14546 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Jordan, C. T. & Lemischka, I. R. Clonal and systemic analysis of long-term hematopoiesis in the mouse. Genes Dev. 4, 220–232 (1990).
  Article CAS PubMed Google Scholar
• Ramalho-Santos, M., Yoon, S., Matsuzaki, Y., Mulligan, R. C. & Melton, D. A. 'Stemness': transcriptional profiling of embryonic and adult stem cells. Science 298, 597–600 (2002).
  Article CAS PubMed Google Scholar
• Ivanova, N. B. et al. A stem cell molecular signature. Science 298, 601–604 (2002).
  Article CAS PubMed Google Scholar
• Akashi, K. et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 101, 383–389 (2003).
  Article CAS PubMed Google Scholar
• Venezia, T. A. et al. Molecular signatures of proliferation and quiescence in hematopoietic stem cells. PLoS Biol. 2, e301 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Roegiers, F. & Jan, Y. N. Asymmetric cell division. Curr. Opin. Cell Biol. 16, 195–205 (2004).
  Article CAS PubMed Google Scholar
• Betschinger, J. & Knoblich, J. A. Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Curr. Biol. 14, R674–R685 (2004).
  Article CAS PubMed Google Scholar
• Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275–280 (2005). This paper shows that some basal cells of the skin epidermis divide in an asymmetric manner (divisional asymmetry), and that this correlates with the unequal distribution of determinants including PAR3, LGN and mINSC in the two daughter cells.
  Article PubMed PubMed Central Google Scholar
• Suda, J., Suda, T. & Ogawa, M. Analysis of differentiation of mouse hemopoietic stem cells in culture by sequential replating of paired progenitors. Blood 64, 393–399 (1984).
  CAS PubMed Google Scholar
• Takano, H., Ema, H., Sudo, K. & Nakauchi, H. Asymmetric division and lineage commitment at the level of hematopoietic stem cells: inference from differentiation in daughter cell and granddaughter cell pairs. J. Exp. Med. 199, 295–302 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Ho, A. D. Kinetics and symmetry of divisions of hematopoietic stem cells. Exp. Hematol. 33, 1–8 (2005).
  Article CAS PubMed Google Scholar
• Xie, T. & Spradling, A. C. A niche maintaining germ line stem cells in the Drosophila ovary. Science 290, 328–330 (2000).
  Article CAS PubMed Google Scholar
• Kiger, A. A., White-Cooper, H. & Fuller, M. T. Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407, 750–754 (2000).
  Article CAS PubMed Google Scholar
• Fleming, W. H. et al. Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. J. Cell Biol. 122, 897–902 (1993).
  Article CAS PubMed Google Scholar
• Cotsarelis, G., Sun, T. T. & Lavker, R. M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61, 1329–1337 (1990).
  Article CAS PubMed Google Scholar
• Tumbar, T. et al. Defining the epithelial stem cell niche in skin. Science 303, 359–363 (2004). In this paper, transgenic expression of H2B–EGFP is used to show that slow-cycling skin epidermal stem cells are primarily located in the hair follicle bulge. This technique, which identifies and allows purification of viable LRCs, should be adaptable for analysis of other adult stem cells and their associated niches.
  Article CAS PubMed Google Scholar
• Zhang, J. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836–841 (2003). N-cadherin was proposed as a critical molecule that anchors HSCs to osteoblasts through homotypic interactions. This study (together with reference 67), also shows that osteoblastic cells are a critical component of the endosteal bone-marrow niche.
  Article CAS PubMed Google Scholar
• Lerner, C. & Harrison, D. E. 5-Fluorouracil spares hemopoietic stem cells responsible for long-term repopulation. Exp. Hematol. 18, 114–118 (1990).
  CAS PubMed Google Scholar
• Spangrude, G. J. & Johnson, G. R. Resting and activated subsets of mouse multipotent hematopoietic stem cells. Proc. Natl Acad. Sci. USA 87, 7433–7437 (1990).
  Article CAS PubMed PubMed Central Google Scholar
• Uchida, N. et al. The unexpected G0/G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood. Blood 89, 465–472 (1997).
  CAS PubMed Google Scholar
• Suda, T., Arai, F. & Hirao, A. Hematopoietic stem cells and their niche. Trends Immunol. 26, 426–433 (2005).
  Article CAS PubMed Google Scholar
• Potten, C. S. & Loeffler, M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110, 1001–1020 (1990).
  CAS PubMed Google Scholar
• Arai, F. et al. Tie2/angiopoietin-1 signalling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149–161 (2004). This paper shows that the ANG1 produced by niche osteoblasts activates TIE2, which maintains HSC quiescence and increases N-cadherin expression, and therefore increases adhesion to the endosteal niche.
  Article CAS PubMed Google Scholar
• Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K. & Barrandon, Y. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 104, 233–245 (2001).
  Article CAS PubMed Google Scholar
• Van Zant, G. Studies of hematopoietic stem cells spared by 5-fluorouracil. J. Exp. Med. 159, 679–690 (1984).
  Article CAS PubMed Google Scholar
• Randall, T. D. & Weissman, I. L. Phenotypic and functional changes induced at the clonal level in hematopoietic stem cells after 5-fluorouracil treatment. Blood 89, 3596–3606 (1997).
  CAS PubMed Google Scholar
• Uchida, N. et al. ABC transporter activities of murine hematopoietic stem cells vary according to their developmental and activation status. Blood 103, 4487–4495 (2004).
  Article CAS PubMed Google Scholar
• Chambers, I. & Smith, A. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23, 7150–7160 (2004).
  Article CAS PubMed Google Scholar
• Cheshier, S. H., Morrison, S. J., Liao, X. & Weissman, I. L. In vivo proliferation and cell cycle kinetics of long-term self- renewing hematopoietic stem cells. Proc. Natl Acad. Sci. USA 96, 3120–3125 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Wilson, A. et al. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. 18, 2747–2763 (2004). This paper provides genetic evidence that differential expression of MYC controls the balance between stem-cell self-renewal and differentiation by regulating entry and exit of HSCs from the endosteal niche.
  Article CAS PubMed PubMed Central Google Scholar
• Murphy, M. J., Wilson, A. & Trumpp, A. More than just proliferation: Myc function in stem cells. Trends Cell Biol. 15, 128–137 (2005).
  Article CAS PubMed Google Scholar
• Patt, H. M. & Maloney, M. A. Bone formation and resorption as a requirement for marrow development. Proc. Soc. Exp. Biol. Med. 140, 205–207 (1972).
  Article CAS PubMed Google Scholar
• Maloney, M. A. & Patt, H. M. On the origin of hematopoietic stem cells after local marrow extirpation. Proc. Soc. Exp. Biol. Med. 149, 94–97 (1975).
  Article CAS PubMed Google Scholar
• Deguchi, K. et al. Excessive extramedullary hematopoiesis in Cbfa1-deficient mice with a congenital lack of bone marrow. Biochem. Biophys. Res. Commun. 255, 352–359 (1999).
  Article CAS PubMed Google Scholar
• Ducy, P., Schinke, T. & Karsenty, G. The osteoblast: a sophisticated fibroblast under central surveillance. Science 289, 1501–1504 (2000).
  Article CAS PubMed Google Scholar
• Karsenty, G. & Wagner, E. F. Reaching a genetic and molecular understanding of skeletal development. Dev. Cell 2, 389–406 (2002).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Gong, J. K. Endosteal marrow: a rich source of hematopoietic stem cells. Science 199, 1443–1445 (1978). This study provides the first functional evidence for the location of HSCs and progenitor cells close to endosteal surfaces of rat bone.
  Article CAS PubMed Google Scholar
• Askenasy, N. & Farkas, D. L. In vivo imaging studies of the effect of recipient conditioning, donor cell phenotype and antigen disparity on homing of haematopoietic cells to the bone marrow. Br. J. Haematol. 120, 505–515 (2003).
  Article PubMed Google Scholar
• Sipkins, D. A. et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 435, 969–973 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Taichman, R. S. & Emerson, S. G. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells 16, 7–15 (1998).
  Article CAS PubMed Google Scholar
• Taichman, R. S. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105, 2631–2639 (2005).
  Article CAS PubMed Google Scholar
• Oostendorp, R. A. et al. Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity. Blood 99, 1183–1189 (2002).
  Article CAS PubMed Google Scholar
• Calvi, L. M. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425, 841–846 (2003).
  Article CAS PubMed Google Scholar
• Chen, D., Zhao, M. & Mundy, G. R. Bone morphogenetic proteins. Growth Factors 22, 233–241 (2004).
  Article CAS PubMed Google Scholar
• Visnjic, D. et al. Conditional ablation of the osteoblast lineage in Col2.3δk transgenic mice. J. Bone Miner. Res. 16, 2222–2231 (2001).
  Article CAS PubMed Google Scholar
• Visnjic, D. et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103, 3258–3264 (2004). This paper shows that conditional ablation of osteoblasts results in a reversible decrease of bone-marrow HSCs and extramedullary haematopoiesis, indicating that osteoblasts are not only required for maintenance of bone-marrow haematopoiesis, but are also an essential component of the niche.
  Article CAS PubMed Google Scholar
• Corral, D. A. et al. Dissociation between bone resorption and bone formation in osteopenic transgenic mice. Proc. Natl Acad. Sci. USA 95, 13835–13840 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Li, W. et al. Primary endothelial cells isolated from the yolk sac and para-aortic splanchnopleura support the expansion of adult marrow stem cells in vitro. Blood 102, 4345–4353 (2003).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Kopp, H. G., Avecilla, S. T., Hooper, A. T. & Rafii, S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda Md.) 20, 349–356 (2005).
  CAS Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Rafii, S., Mohle, R., Shapiro, F., Frey, B. M. & Moore, M. A. Regulation of hematopoiesis by microvascular endothelium. Leuk. Lymphoma 27, 375–386 (1997).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Rafii, S. et al. Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood 86, 3353–3363 (1995).
  CAS PubMed Google Scholar
• Delehanty, L. L. et al. Stromal inhibition of megakaryocytic differentiation is associated with blockade of sustained Rap1 activation. Blood 101, 1744–1751 (2003).
  Article CAS PubMed Google Scholar
• Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B. I. & Nagasawa, T. Cellular niches controlling B lymphocyte behaviour within bone marrow during development. Immunity 20, 707–718 (2004).
  Article CAS PubMed Google Scholar
• Hirose, J. et al. A developing picture of lymphopoiesis in bone marrow. Immunol. Rev. 189, 28–40 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Papayannopoulou, T. Bone marrow homing: the players, the playfield, and their evolving roles. Curr. Opin. Hematol. 10, 214–219 (2003).
  Article PubMed Google Scholar
• Lapidot, T., Dar, A. & Kollet, O. How do stem cells find their way home? Blood 106, 1901–1910 (2005).
  Article CAS PubMed Google Scholar
• Cancelas, J. A. et al. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Nature Med. 11, 886–891 (2005).
  Article CAS PubMed Google Scholar
• Lapidot, T. & Petit, I. Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp. Hematol. 30, 973–981 (2002).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Potocnik, A. J., Brakebusch, C. & Fassler, R. Fetal and adult hematopoietic stem cells require β1 integrin function for colonizing fetal liver, spleen, and bone marrow. Immunity 12, 653–663 (2000).
  Article CAS PubMed Google Scholar
• Nilsson, S. K. et al. Hyaluronan is synthesized by primitive hemopoietic cells, participates in their lodgment at the endosteum following transplantation, and is involved in the regulation of their proliferation and differentiation in vitro. Blood 101, 856–862 (2003).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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). The authors show that CXCL12 has an important role in colonization of the bone marrow by HSCs.
  Article CAS PubMed Google Scholar
• Ponomaryov, T. et al. Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J. Clin. Invest. 106, 1331–1339 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Wright, D. E., Bowman, E. P., Wagers, A. J., Butcher, E. C. & Weissman, I. L. Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J. Exp. Med. 195, 1145–1154 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Gu, Y. et al. Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science 302, 445–449 (2003).
  Article CAS PubMed Google Scholar
• Moore, K. A. Recent advances in defining the hematopoietic stem cell niche. Curr. Opin. Hematol. 11, 107–111 (2004).
  Article CAS PubMed Google Scholar
• Artavanis-Tsakonas, S., Rand, M. D. & Lake, R. J. Notch signalling: cell fate control and signal integration in development. Science 284, 770–776 (1999).
  Article CAS PubMed Google Scholar
• Reya, T. & Clevers, H. Wnt signalling in stem cells and cancer. Nature 434, 843–850 (2005).
  Article CAS PubMed Google Scholar
• Radtke, F., Wilson, A., Mancini, S. J. & MacDonald, H. R. Notch regulation of lymphocyte development and function. Nature Immunol. 5, 247–253 (2004).
  Article CAS Google Scholar
• Duncan, A. W. et al. Integration of Notch and Wnt signalling in hematopoietic stem cell maintenance. Nature Immunol. 6, 314–322 (2005).
  Article CAS Google Scholar
• Varnum-Finney, B. et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signalling. Nature Med. 6, 1278–1281 (2000).
  Article CAS PubMed Google Scholar
• Stier, S., Cheng, T., Dombkowski, D., Carlesso, N. & Scadden, D. T. Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favours lymphoid over myeloid lineage outcome. Blood 99, 2369–2378 (2002).
  Article CAS PubMed Google Scholar
• Han, H. et al. Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision. Int. Immunol. 14, 637–645 (2002).
  Article CAS PubMed Google Scholar
• Mancini, S. J. et al. Jagged1-dependent Notch signalling is dispensable for hematopoietic stem cell self-renewal and differentiation. Blood 105, 2340–2342 (2005).
  Article CAS PubMed Google Scholar
• Radtke, F. et al. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10, 547–558 (1999).
  Article CAS PubMed Google Scholar
• Saito, T. et al. Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity 18, 675–685 (2003).
  Article CAS PubMed Google Scholar
• Denhardt, D. T. & Guo, X. Osteopontin: a protein with diverse functions. FASEB J. 7, 1475–1482 (1993).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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 Sld mutant. Cell 64, 1025–1035 (1991).
  Article CAS PubMed Google Scholar
• Lyman, S. D. & Jacobsen, S. E. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 91, 1101–1134 (1998).
  CAS PubMed Google Scholar
• Miyazawa, K. et al. Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form. Blood 85, 641–649 (1995).
  CAS PubMed Google Scholar
• Kinashi, T. & Springer, T. A. Steel factor and c-kit regulate cell-matrix adhesion. Blood 83, 1033–1038 (1994).
  CAS PubMed Google Scholar
• Kovach, N. L., Lin, N., Yednock, T., Harlan, J. M. & Broudy, V. C. Stem cell factor modulates avidity of α4 β1 and α5 β1 integrins expressed on hematopoietic cell lines. Blood 85, 159–167 (1995).
  CAS PubMed Google Scholar
• Driessen, R. L., Johnston, H. M. & Nilsson, S. K. Membrane-bound stem cell factor is a key regulator in the initial lodgment of stem cells within the endosteal marrow region. Exp. Hematol. 31, 1284–1291 (2003).
  Article CAS PubMed Google Scholar
• Lotinun, S., Evans, G. L., Turner, R. T. & Oursler, M. J. Deletion of membrane-bound steel factor results in osteopenia in mice. J. Bone Miner. Res. 20, 644–652 (2005).
  Article CAS PubMed Google Scholar
• Radice, G. L. et al. Developmental defects in mouse embryos lacking N-cadherin. Dev. Biol. 181, 64–78 (1997).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Cheng, T. et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287, 1804–1808 (2000).
  Article CAS PubMed Google Scholar
• Cheng, T., Shen, H., Rodrigues, N., Stier, S. & Scadden, D. T. Transforming growth factor β1 mediates cell-cycle arrest of primitive hematopoietic cells independent of p21(Cip1/Waf1) or p27(Kip1). Blood 98, 3643–3649 (2001).
  Article CAS PubMed Google Scholar
• Wu, S. et al. Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 22, 351–360 (2003).
  Article CAS PubMed Google Scholar
• Reiss, K. et al. ADAM10 cleavage of N-cadherin and regulation of cell–cell adhesion and β-catenin nuclear signalling. EMBO J. 24, 742–752 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Ito, K. et al. Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of β-catenin from cell–cell contacts. Oncogene 18, 7080–7090 (1999).
  Article CAS PubMed Google Scholar
• Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003). This paper, together with reference 126, provides evidence of a positive role for WNT signalling in HSC self-renewal, whereas differentiation (at least in vitro ) is inhibited.
  Article CAS PubMed Google Scholar
• Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409–414 (2003).
  Article CAS PubMed Google Scholar
• Cobas, M. et al. β-catenin is dispensable for hematopoiesis and lymphopoiesis. J. Exp. Med. 199, 221–229 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Friedl, P. & Storim, J. Diversity in immune-cell interactions: states and functions of the immunological synapse. Trends Cell Biol. 14, 557–567 (2004).
  Article CAS PubMed Google Scholar
• Powell, K. It's the ecology, stupid. Nature 435, 268–270 (2005).
  Article CAS PubMed Google Scholar
• Sorrentino, B. P. Clinical strategies for expansion of haematopoietic stem cells. Nature Rev. Immunol. 4, 878–888 (2004).
  Article CAS Google Scholar
• Ploemacher, R. E. Stem cells: characterization and measurement. Baillieres Clin. Haematol. 10, 429–444 (1997).
  Article CAS PubMed Google Scholar
• Morrison, S. J., Uchida, N. & Weissman, I. L. The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11, 35–71 (1995).
  Article CAS PubMed Google Scholar
• Visser, J. W., Bauman, J. G., Mulder, A. H., Eliason, J. F. & de Leeuw, A. M. Isolation of murine pluripotent hemopoietic stem cells. J. Exp. Med. 159, 1576–1590 (1984).
  Article CAS PubMed Google Scholar
• Bunting, K. D. ABC Transporters as phenotypic markers and functional regulators of stem cells. Stem Cells 20, 11–20 (2002).
  Article CAS PubMed Google Scholar
• Goodell, M. A., McKinney-Freeman, S. & Camargo, F. D. Isolation and characterization of side population cells. Methods Mol. Biol. 290, 343–352 (2005).
  PubMed Google Scholar
• Uchida, N., Dykstra, B., Lyons, K. J., Leung, F. Y. & Eaves, C. J. 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. 31, 1338–1347 (2003).
  Article CAS PubMed Google Scholar
• Camargo, F. D., Chambers, S. M., Drew, E., McNagny, K. M. & Goodell, M. A. Hematopoietic stem cells do not engraft with absolute efficiencies. Blood 107, 501–507 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Bradford, G. B., Williams, B., Rossi, R. & Bertoncello, I. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp. Hematol. 25, 445–453 (1997).
  CAS PubMed Google Scholar
• Komori, T. et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89, 755–764 (1997).
  Article CAS PubMed Google Scholar
• Otto, F. et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765–771 (1997).
  Article CAS PubMed Google Scholar
• Adams, G. D. et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 28 Dec 2005 (doi:10.1038/nature04247).