Information de reference pour ce titreAccession Number: | 00006056-200310230-00047.
|
Author: | Calvi, L. M. 1*; Adams, G. B. 3*; Weibrecht, K. W. 3; Weber, J. M. 1; Olson, D. P. 3; Knight, M. C. 4; Martin, R. P. 3; Schipani, E. 4; Divieti, P. 4; Bringhurst, F. R. 4; Milner, L. A. 2; Kronenberg, H. M. 4; Scadden, D. T. 3
|
Institution: | (1)Endocrine Unit, Department of Medicine, and (2)Department of Pediatrics, Center for Human Genetics and Molecular Pediatric Disease, University of Rochester School of Medicine, Rochester, New York 14642, USA (3)Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, and (4)Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, Massachusetts, USA
|
Title: | Osteoblastic cells regulate the haematopoietic stem cell niche.[Letter]
|
Source: | Nature. 425(6960):841-846, October 23, 2003.
|
Abstract: | Stem cell fate is influenced by specialized microenvironments that remain poorly defined in mammals 1-3. To explore the possibility that haematopoietic stem cells derive regulatory information from bone, accounting for the localization of haematopoiesis in bone marrow, we assessed mice that were genetically altered to produce osteoblast-specific, activated PTH/PTHrP receptors (PPRs) 4. Here we show that PPR-stimulated osteoblastic cells that are increased in number produce high levels of the Notch ligand jagged 1 and support an increase in the number of haematopoietic stem cells with evidence of Notch1 activation in vivo. Furthermore, ligand-dependent activation of PPR with parathyroid hormone (PTH) increased the number of osteoblasts in stromal cultures, and augmented ex vivo primitive haematopoietic cell growth that was abrogated by [gamma]-secretase inhibition of Notch activation. An increase in the number of stem cells was observed in wild-type animals after PTH injection, and survival after bone marrow transplantation was markedly improved. Therefore, osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation. Niche constituent cells or signalling pathways provide pharmacological targets with therapeutic potential for stem-cell-based therapies.
(C) 2003 Nature Publishing Group
|
References: | 1. Spradling, A., Drummond-Barbosa, D. & Kai, T. Stem cells find their niche. Nature 414, 98-104 (2001).
2. 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).
3. Tran, J., Brenner, T. J. & DiNardo, S. Somatic control over the germline stem cell lineage during Drosophila spermatogenesis. Nature 407, 754-757 (2000).
4. Calvi, L. M. et al. Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone. J. Clin. Invest. 107, 277-286 (2001).
5. 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).
6. Gong, J. K. Endosteal marrow: a rich source of hematopoietic stem cells. Science 199, 1443-1445 (1978).
7. Cui, Y. F., Lord, B. I., Woolford, L. B. & Testa, N. G. The relative spatial distribution of in vitro-CFCs in the bone marrow, responding to specific growth factors. Cell Prolif. 29, 243-257 (1996).
8. Lord, B. I. The architecture of bone marrow cell populations. Int. J. Cell Cloning 8, 317-331 (1990).
9. 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).
10. Taichman, R. S., Reilly, M. J. & Emerson, S. G. Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. Blood 87, 518-524 (1996).
11. Taichman, R., Reilly, M., Verma, R., Ehrenman, K. & Emerson, S. Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors. Br. J. Haematol. 112, 438-448 (2001).
12. Ploemacher, R. E., van der Sluijs, J. P., van Beurden, C. A., Baert, M. R. & Chan, P. L. Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse. Blood 78, 2527-2533 (1991).
13. 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).
14. Varnum-Finney, B., Brashem-Stein, C. & Bernstein, I. D. Combined effects of Notch signalling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability. Blood 101, 1784-1789 (2003).
15. Varnum-Finney, B. et al. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signalling. Nature Med. 6, 1278-1281 (2000).
16. Karanu, F. N. et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J. Exp. Med. 192, 1365-1372 (2000).
17. Karanu, F. N. et al. Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells. Blood 97, 1960-1967 (2001).
18. Li, L. et al. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity 8, 43-55 (1998).
19. Pereira, R. M., Delany, A. M., Durant, D. & Canalis, E. Cortisol regulates the expression of Notch in osteoblasts. J. Cell. Biochem. 85, 252-258 (2002).
20. Huppert, S. S. et al. Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1. Nature 405, 966-970 (2000).
21. Wolfe, M. S. et al. Peptidomimetic probes and molecular modeling suggest that Alzheimer's [gamma]-secretase is an intramembrane-cleaving aspartyl protease. Biochemistry 38, 4720-4727 (1999).
22. Zhang, J. et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425, 836-841 (2003).
23. Schofield, R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4, 7-25 (1978).
24. Taichman, R. S., Reilly, M. J. & Emerson, S. G. The hematopoietic microenvironment: osteoblasts and the hematopoietic microenvironment. Hematology 4, 421-426 (2000).
25. Cheng, T. et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287, 1804-1808 (2000).
26. Giri, N., Kaushiva, A., Wu, T., Sellers, S. E. & Tisdale, J. F. The effects of SCF/G-CSF prestimulation on radiation sensitivity and engraftment in nonmyeloablated murine hosts. Exp. Hematol. 29, 779-785 (2001).
|
Language: | English.
|
Document Type: | Letters to Nature.
|
Journal Subset: | Life Sciences. Physical Science & Engineering.
|
ISSN: | 0028-0836
|
NLM Journal Code: | 0410462, nsc
|
Annotation(s) | |
|
|