The bone marrow at the crossroads of blood and immunity

Nature Reviews Immunology

Volumn 12, Issue 1, 2012, Pages 49-60

  Mercier, Francois E ^a,b   Ragu, Christine ^a,b   Scadden, David T ^a,b  

^a MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^b Harvard University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN 1; B CELL ACTIVATING FACTOR; CD146 ANTIGEN; CD150 ANTIGEN; CD34 ANTIBODY; CD38 ANTIGEN; CD44V ANTIGEN; CD48 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; FIBRINOGEN RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; NESTIN; NEUROGENIC DIFFERENTIATION FACTOR; OSTEOCLAST DIFFERENTIATION FACTOR; STEM CELL ANTIGEN 1; THROMBOPOIETIN; TUMOR NECROSIS FACTOR; VASCULAR CELL ADHESION MOLECULE 1;

ADAPTIVE IMMUNITY; ADIPOCYTE; ADRENERGIC SYSTEM; BONE MARROW; BONE MARROW CELL; CELL DIFFERENTIATION; CELL INTERACTION; DENDRITIC CELL; FLOW CYTOMETRY; GRANULOCYTE; HEMATOPOIETIC STEM CELL; IMMUNITY; IMMUNOCOMPETENT CELL; LYMPHOPOIESIS; MACROPHAGE; MESENCHYME CELL; MYELOID DENDRITIC CELL; OSTEOBLAST; OSTEOCLAST; OXYGENATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ANIMALS; BONE MARROW; BONE MARROW CELLS; CELL DIFFERENTIATION; HEMATOPOIETIC STEM CELLS; HUMANS; IMMUNITY; STEM CELL NICHE;

EID: 84555189736     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3132     Document Type: Review

References (125)

1. Scadden, D. T. The stem-cell niche as an entity of action. Nature 441, 1075-1079 (2006). (Pubitemid 43990719)
2. Schofield, R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4, 7-25 (1978). (Pubitemid 8376317)
3. Jones, D. L. & Wagers, A. J. No place like home: anatomy and function of the stem cell niche. Nature Rev. Mol. Cell Biol. 9, 11-21 (2008).
4. Dzierzak, E. & Speck, N. A. Of lineage and legacy: the development of mammalian hematopoietic stem cells. Nature Immunol. 9, 129-136 (2008).
5. 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). (Pubitemid 40884400)
6. O'Malley, D. P. Benign extramedullary myeloid proliferations. Mod. Pathol. 20, 405-415 (2007). (Pubitemid 46482374)
7. Morita, Y. et al. Functional characterization of hematopoietic stem cells in the spleen. Exp. Hematol. 39, 351-359 (2011).
8. Calvi, L. M. et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425, 841-846 (2003). (Pubitemid 37351468)
9. North, T. E. et al. Hematopoietic stem cell development is dependent on blood flow. Cell 137, 736-748 (2009).
10. Adamo, L. et al. Biomechanical forces promote embryonic haematopoiesis. Nature 459, 1131-1135 (2009).
11. Lancrin, C. et al. Blood cell generation from the hemangioblast. J. Mol. Med. 88, 167-172 (2010).
12. Sipkins, D. A. et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 435, 969-973 (2005). (Pubitemid 40896324)
13. Rafii, S., Mohle, R., Shapiro, F., Frey, B. M. & Moore, M. A. Regulation of hematopoiesis by microvascular endothelium. Leuk. Lymphoma 27, 375-386 (1997). (Pubitemid 28029900)
14. Mazo, I. B. et al. Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J. Exp. Med. 188, 465-474 (1998). (Pubitemid 28369136)
15. Kopp, H. G., Hooper, A. T., Avecilla, S. T. & Rafii, S. Functional heterogeneity of the bone marrow vascular niche. Ann. NY Acad. Sci. 1176, 47-54 (2009).
16. Ellis, S. L. et al. The relationship between bone, hemopoietic stem cells, and vasculature. Blood 118, 1516-1524 (2011).
17. Butler, J. M. et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6, 251-264 (2010).
18. Kobayashi, H. et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nature Cell Biol. 12, 1046-1056 (2010).
19. Sacchetti, B. et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131, 324-336 (2007). (Pubitemid 47592917)
20. Mendez-Ferrer, S. et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466, 829-834 (2010).
21. 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). (Pubitemid 44894948)
22. Omatsu, Y. et al. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 33, 387-399 (2010).
23. Naveiras, O. et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460, 259-263 (2009).
24. Walkley, C. R. et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor γ deficiency. Cell 129, 1097-1110 (2007). (Pubitemid 46908696)
25. Grassinger, J., Haylock, D. N., Williams, B., Olsen, G. H. & Nilsson, S. K. Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential. Blood 116, 3185-3196 (2010).
26. Lord, B. I. & Hendry, J. H. The distribution of haemopoietic colony-forming units in the mouse femur, and its modification by X rays. Br. J. Radiol. 45, 110-115 (1972).
27. Taichman, R. S. Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche. Blood 105, 2631-2639 (2005). (Pubitemid 40446251)
28. 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). (Pubitemid 34525422)
29. Fleming, H. E. et al. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell 2, 274-283 (2008). (Pubitemid 351298592)
30. Yoshihara, H. et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 1, 685-697 (2007). (Pubitemid 350215333)
31. Qian, H. et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell 1, 671-684 (2007). (Pubitemid 350215331)
32. Arai, F. et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118, 149-161 (2004). (Pubitemid 38962572)
33. Jung, Y. et al. Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110, 82-90 (2007). (Pubitemid 47026822)
34. Raaijmakers, M. H. et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 464, 852-857 (2010).
35. Ferraro, F. et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci. Transl. Med. 3, 104ra101 (2011).
36. Jacome-Galarza, C. E., Lee, S. K., Lorenzo, J. A. & Aguila, H. L. Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow. J. Bone Miner. Res. 26, 1207-1216 (2011).
37. 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). (Pubitemid 41002897)
38. 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). (Pubitemid 41129584)
39. Adams, G. B. et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 439, 599-603 (2006). (Pubitemid 43185384)
40. Kollet, O. et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Med. 12, 657-664 (2006). (Pubitemid 43865234)
41. Lymperi, S., Ersek, A., Ferraro, F., Dazzi, F. & Horwood, N. J. Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo. Blood 117, 1540-1549 (2011).
42. Miyamoto, K. et al. Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. J. Exp. Med. 208, 2175-2181 (2011).
43. Chow, A. et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J. Exp. Med. 208, 261-271 (2011).
44. Winkler, I. G. et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 116, 4815-4828 (2010).
45. Christopher, M. J., Rao, M., Liu, F., Woloszynek, J. R. & Link, D. C. Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice. J. Exp. Med. 208, 251-260 (2011).
46. Morita, Y., Ema, H. & Nakauchi, H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 207, 1173-1182 (2010).
47. Dykstra, B. et al. Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell 1, 218-229 (2007). (Pubitemid 47215588)
48. Challen, G. A., Boles, N. C., Chambers, S. M. & Goodell, M. A. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-β1. Cell Stem Cell 6, 265-278 (2010).
49. Beerman, I. et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl Acad. Sci. USA 107, 5465-5470 (2010).
50. Weber, J. M. & Calvi, L. M. Notch signaling and the bone marrow hematopoietic stem cell niche. Bone 46, 281-285 (2010).
51. Zhu, J. et al. Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. Blood 109, 3706-3712 (2007). (Pubitemid 46641719)
52. Mansour, A. et al. Osteoclast activity modulates B-cell development in the bone marrow. Cell Res. 21, 1102-1115 (2011).
53. Tokoyoda, K., Egawa, T., Sugiyama, T., Choi, B. I. & Nagasawa, T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity 20, 707-718 (2004). (Pubitemid 38757441)
54. Peschon, J. J. et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180, 1955-1960 (1994).
55. Pereira, J. P., An, J., Xu, Y., Huang, Y. & Cyster, J. G. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nature Immunol. 10, 403-411 (2009).
56. Cariappa, A., Chase, C., Liu, H., Russell, P. & Pillai, S. Naive recirculating B cells mature simultaneously in the spleen and bone marrow. Blood 109, 2339-2345 (2007). (Pubitemid 46425873)
57. Sapoznikov, A. et al. Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches. Nature Immunol. 9, 388-395 (2008). (Pubitemid 351405108)
58. Feuerer, M. et al. Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nature Med. 9, 1151-1157 (2003). (Pubitemid 37173699)
59. Benner, R., Meima, F., van der Meulen, G. M. & van Muiswinkel, W. B. Antibody formation in mouse bone marrow. I. Evidence for the development of plaque-forming cells in situ. Immunology 26, 247-255 (1974).
60. Cassese, G. et al. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J. Immunol. 171, 1684-1690 (2003). (Pubitemid 36966450)
61. Benson, M. J. et al. Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J. Immunol. 180, 3655-3659 (2008).
62. Nie, Y. et al. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J. Exp. Med. 200, 1145-1156 (2004). (Pubitemid 39507054)
63. Chu, V. T. et al. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nature Immunol. 12, 151-159 (2011).
64. Winter, O. et al. Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood 116, 1867-1875 (2010).
65. Ma, Q., Jones, D. & Springer, T. A. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity 10, 463-471 (1999). (Pubitemid 29205482)
66. Hattori, K., Heissig, B. & Rafii, S. The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk. Lymphoma 44, 575-582 (2003). (Pubitemid 36304814)
67. Tokoyoda, K. et al. Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity 30, 721-730 (2009).
68. Tokoyoda, K., Hauser, A. E., Nakayama, T. & Radbruch, A. Organization of immunological memory by bone marrow stroma. Nature Rev. Immunol. 10, 193-200 (2010).
69. Mazo, I. B. et al. Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 22, 259-270 (2005). (Pubitemid 40255716)
70. Fujisaki, J. et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature 474, 216-219 (2011).
71. Wilkins, B. S. Histology of normal haemopoiesis: bone marrow histology I. J. Clin. Pathol. 45, 645-649 (1992).
72. Eash, K. J., Greenbaum, A. M., Gopalan, P. K. & Link, D. C. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J. Clin. Invest. 120, 2423-2431 (2010).
73. Kohler, A. et al. G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood 117, 4349-4357 (2011).
74. Wang, Y. et al. CCR2 and CXCR4 regulate peripheral blood monocyte pharmacodynamics and link to efficacy in experimental autoimmune encephalomyelitis. J. Inflamm. 6, 32 (2009).
75. 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). (Pubitemid 47175697)
76. Winkler, I. G. et al. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood 116, 375-385 (2010).
77. Eliasson, P. & Jonsson, J. I. The hematopoietic stem cell niche: low in oxygen but a nice place to be. J. Cell Physiol. 222, 17-22 (2009).
78. Takubo, K. et al. Regulation of the HIF-1α level is essential for hematopoietic stem cells. Cell Stem Cell 7, 391-402 (2010).
79. Cipolleschi, M. G., Dello Sbarba, P. & Olivotto, M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood 82, 2031-2037 (1993). (Pubitemid 23293984)
80. Eliasson, P. et al. Hypoxia mediates low cell-cycle activity and increases the proportion of long-term-reconstituting hematopoietic stem cells during in vitro culture. Exp. Hematol. 38, 301-310 (2010).
81. Wheaton, W. W. & Chandel, N. S. Hypoxia. 2. Hypoxia regulates cellular metabolism. Am. J. Physiol. Cell Physiol. 300, C385-C393 (2011).
82. Simsek, T. et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 7, 380-390 (2010).
83. Kirito, K., Fox, N., Komatsu, N. & Kaushansky, K. Thrombopoietin enhances expression of vascular endothelial growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1α. Blood 105, 4258-4263 (2005). (Pubitemid 40720771)
84. Gerber, H. P. et al. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature 417, 954-958 (2002).
85. Jogi, A. et al. Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc. Natl Acad. Sci. USA 99, 7021-7026 (2002). (Pubitemid 34526250)
86. Mazumdar, J. et al. O2 regulates stem cells through Wnt/β-catenin signalling. Nature Cell Biol. 12, 1007-1013 (2010).
87. Ceradini, D. J. et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Med. 10, 858-864 (2004). (Pubitemid 39070860)
88. Wang, Y. et al. The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development. J. Clin. Invest. 117, 1616-1626 (2007). (Pubitemid 46871346)
89. Pedersen, M. et al. Stem cell factor induces HIF-1α at normoxia in hematopoietic cells. Biochem. Biophys. Res. Commun. 377, 98-103 (2008).
90. Bakker, W. J., Harris, I. S. & Mak, T. W. FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2. Mol. Cell 28, 941-953 (2007). (Pubitemid 350297029)
91. Kojima, H. et al. Differentiation stage-specific requirement in hypoxia-inducible factor-1α-regulated glycolytic pathway during murine B cell development in bone marrow. J. Immunol. 184, 154-163 (2009).
92. Kojima, H. et al. Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1α-deficient chimeric mice. Proc. Natl Acad. Sci. USA 99, 2170-2174 (2002). (Pubitemid 34169033)
93. Fukuda, R. et al. Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J. Biol. Chem. 277, 38205-38211 (2002). (Pubitemid 35154674)
94. Mignini, F., Streccioni, V. & Amenta, F. Autonomic innervation of immune organs and neuroimmune modulation. Auton. Autacoid Pharmacol. 23, 1-25 (2003). (Pubitemid 36917752)
95. Mendez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452, 442-447 (2008). (Pubitemid 351450836)
96. Elefteriou, F. et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434, 514-520 (2005). (Pubitemid 40477060)
97. Schajnovitz, A. et al. CXCL12 secretion by bone marrow stromal cells is dependent on cell contact and mediated by connexin-43 and connexin-45 gap junctions. Nature Immunol. 12, 391-398 (2011).
98. Katayama, Y. et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124, 407-421 (2006). (Pubitemid 43121987)
99. Lapid, K., Vagima, Y., Kollet, O. & Lapidot, T. Egress and mobilization of hematopoietic stem and progenitor cells. StemBook [online], http://www. stembook.org/node/558 (2009).
100. Spiegel, A. et al. Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling. Nature Immunol. 8, 1123-1131 (2007). (Pubitemid 47423760)
101. Nance, D. M. & Sanders, V. M. Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav. Immun. 21, 736-745 (2007). (Pubitemid 47002215)
102. Harrison, D. E. & Lerner, C. P. Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil. Blood 78, 1237-1240 (1991).
103. Birnberg, T. et al. Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29, 986-997 (2008).
104. Keren, Z. et al. B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging. Blood 117, 3104-3112 (2011).
105. 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). (Pubitemid 33101591)
106. Abkowitz, J. L., Robinson, A. E., Kale, S., Long, M. W. & Chen, J. Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102, 1249-1253 (2003). (Pubitemid 36988029)
107. Bhattacharya, D. et al. Niche recycling through division-independent egress of hematopoietic stem cells. J. Exp. Med. 206, 2837-2850 (2009).
108. Sato, T. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415-418 (2011).
109. Baldridge, M. T., King, K. Y. & Goodell, M. A. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 32, 57-65 (2011).
110. Baldridge, M. T., King, K. Y., Boles, N. C., Weksberg, D. C. & Goodell, M. A. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature 465, 793-797 (2010).
111. Essers, M. A. et al. IFNα activates dormant haematopoietic stem cells in vivo. Nature 458, 904-908 (2009).
112. Greenbaum, A. M. & Link, D. C. Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia 25, 211-217 (2010).
113. Shi, C. et al. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating Toll-like receptor ligands. Immunity 34, 590-601 (2011).
114. Singer, N. G. & Caplan, A. I. Mesenchymal stem cells: mechanisms of inflammation. Annu. Rev. Pathol. 6, 457-478 (2011).
115. Francois, M. et al. Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood 114, 2632-2638 (2009).
116. Pober, J. S. & Sessa, W. C. Evolving functions of endothelial cells in inflammation. Nature Rev. Immunol. 7, 803-815 (2007). (Pubitemid 47480307)
117. Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E. & Orkin, S. H. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell 129, 1081-1095 (2007). (Pubitemid 46908695)
118. McCarthy, K. F., Ledney, G. D. & Mitchell, R. A deficiency of hematopoietic stem cells in steel mice. Cell Tissue Kinet. 10, 121-126 (1977). (Pubitemid 8053919)
119. Varnum-Finney, B. et al. Notch2 governs the rate of generation of mouse long-and short-term repopulating stem cells. J. Clin. Invest. 121, 1207-1216 (2011).
120. Maillard, I. et al. Canonical Notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell 2, 356-366 (2008). (Pubitemid 351455243)
121. Cobas, M. et al. β-catenin is dispensable for hematopoiesis and lymphopoiesis. J. Exp. Med. 199, 221-229 (2004).
122. Visnjic, D. et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103, 3258-3264 (2004). (Pubitemid 38525648)
123. Zhang, J. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836-841 (2003). (Pubitemid 37351467)
124. 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). (Pubitemid 47215590)
125. Wu, J. Y. et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gsα-dependent signaling pathways. Proc. Natl Acad. Sci. USA 105, 16976-16981 (2008).