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Blood, 1 August 2008, Vol. 112, No. 3, pp. 519-531. Prepublished online as a Blood First Edition Paper on May 2, 2008; DOI 10.1182/blood-2008-01-133710. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-01-133710v1 112/3/519    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mayack, S. R Articles by Wagers, A. J Search for Related Content PubMed PubMed Citation Articles by Mayack, S. R Articles by Wagers, A. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 15, 2008 Accepted March 25, 2008 Osteolineage niche cells initiate hematopoietic stem cell mobilization Shane R Mayack and Amy J Wagers* Developmental and Stem Cell Biology, Joslin Diabetes Center, Boston, MA, United States * Corresponding author; email: amy.wagers{at}joslin.harvard.edu. Recent studies using gene-targeted and hormone-treated mice have implicated bone-lining osteoblasts as important regulators of hematopoietic stem cell (HSC) self-renewal and differentiation; however, as much of the evidence supporting this notion derives from indirect in vivo experiments, which are unavoidably complicated by the presence of other cell types within the complex bone marrow milieu, the sufficiency of osteoblasts in modulating HSC activity has remained controversial 1. To address this issue, we prospectively isolated mouse osteoblasts, using a novel, flow cytometry-based approach, and directly tested their activity as HSC niche cells and their role in cyclophosphamide/G-CSF (Cy/G) induced HSC proliferation and mobilization. We found that osteoblasts expand rapidly following Cy/G treatment and exhibit significant phenotypic and functional changes that directly influence their ability to support HSC proliferation and maintenance of reconstituting potential. Furthermore, these effects of mobilization on osteoblast number and function depend on the function of ATM, the product of the ataxia telangiectasia mutated (Atm) gene, demonstrating a new role for this kinase in supporting stem cell niche activity. Taken together, these studies demonstrate that signals from osteoblasts can directly initiate and modulate HSC proliferation in the context of mobilization. More broadly, this work establishes that direct interaction with the osteolineage niche cell itself - in the absence of additional environmental inputs - is sufficient to modulate stem cell activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Osteoblasts: yes, they can Daniel Lucas and Paul S. Frenette Blood 2008 112: 455. [Full Text] [PDF] This article has been cited by other articles: M. Jeong, Z.-H. Piao, M. S. Kim, S. H. Lee, S. Yun, H.-n. Sun, S. R. Yoon, J. W. Chung, T.-D. Kim, J. H. Jeon, et al. Thioredoxin-Interacting Protein Regulates Hematopoietic Stem Cell Quiescence and Mobilization under Stress Conditions J. Immunol., August 15, 2009; 183(4): 2495 - 2505. [Abstract] [Full Text] [PDF] S. W. Lane, D. T. Scadden, and D. G. Gilliland The leukemic stem cell niche: current concepts and therapeutic opportunities Blood, August 6, 2009; 114(6): 1150 - 1157. [Abstract] [Full Text] [PDF] A. L. Hazen, M. J. Smith, C. Desponts, O. Winter, K. Moser, and W. G. Kerr SHIP is required for a functional hematopoietic stem cell niche Blood, March 26, 2009; 113(13): 2924 - 2933. [Abstract] [Full Text] [PDF]

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