Osteoblastic cells regulate the haematopoietic stem cell niche

L. M. Calvi, G. B. Adams, K. W. Weibrecht, J. M. Weber, D. P. Olson, M. C. Knight, R. P. Martin, E. Schipani, P. Divieti, F. R. Bringhurst, L. A. Milner, H. M. Kronenberg and D. T. Scadden ()
Additional contact information
L. M. Calvi: Center for Human Genetics and Molecular Pediatric Disease, University of Rochester School of Medicine
G. B. Adams: Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School
K. W. Weibrecht: Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School
J. M. Weber: Center for Human Genetics and Molecular Pediatric Disease, University of Rochester School of Medicine
D. P. Olson: Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School
M. C. Knight: Massachusetts General Hospital, Harvard Medical School
R. P. Martin: Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School
E. Schipani: Massachusetts General Hospital, Harvard Medical School
P. Divieti: Massachusetts General Hospital, Harvard Medical School
F. R. Bringhurst: Massachusetts General Hospital, Harvard Medical School
L. A. Milner: University of Rochester School of Medicine
H. M. Kronenberg: Massachusetts General Hospital, Harvard Medical School
D. T. Scadden: Center for Regenerative Medicine and Technology, Partners AIDS Research Center, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School

Nature, 2003, vol. 425, issue 6960, 841-846

Abstract: Abstract Stem cell fate is influenced by specialized microenvironments that remain poorly defined in mammals1,2,3. 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 γ-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.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature02040 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:425:y:2003:i:6960:d:10.1038_nature02040

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02040

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().