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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-07-2286. This Article Full Text (PDF) All Versions of this Article: 2002-07-2286v1 102/1/118    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 Dybedal, I. Articles by Jacobsen, S. E. W Search for Related Content PubMed PubMed Citation Articles by Dybedal, I. Articles by Jacobsen, S. E. W Social Bookmarking                   What's this? Submitted July 29, 2002 Accepted February 24, 2003 Human reconstituting hematopoietic stem cells up-regulate Fas expression upon active cell cycling but remain resistant to Fas-induced suppression Ingunn Dybedal, Liping Yang, David Bryder, Ingbritt Aastrand-Grundstrom, Karin Leandersson, and Sten Eirik W Jacobsen* Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, University Hospital of Lund, Lund, Sweden * Corresponding author; email: sten.jacobsen{at}stemcell.lu.se. The Fas receptor and its ligand have been implicated in mediating the bone marrow (BM) suppression observed in graft versus host disease and a number of other BM failure syndromes. However, previous studies have suggested that Fas is probably not expressed on human hematopoietic stem cells (HSC), but up-regulated as a consequence of their commitment and differentiation, suggesting that progenitors or differentiated blood cells rather than HSC are the targets of Fas-mediated suppression. The present studies confirm that candidate HSC in human cord blood and BM lack constitutive expression of Fas, but demonstrate that Fas expression on CD34+ progenitor and stem cells is correlated to their cell cycle and activation status. Using recently developed in vitro conditions promoting HSC self-renewing divisions, Fas was up-regulated on virtually all HSC capable of multilineage reconstituting NOD-SCID mice in vivo, as well as on long-term culture-initiating cells (LTC-IC). Similarly, in vivo cycling of NOD-SCID repopulating cells upon transplantation, resulted in up-regulation of Fas expression. However, repopulating HSC expressing high levels of Fas remained highly resistant to Fas-mediated suppression, and HSC function was only compromised upon co-activation with tumor necrosis factor. Thus, reconstituting human HSC up-regulate Fas expression upon active cycling, demonstrating that HSC could be targets for Fas-mediated BM suppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Pearl-Yafe, J. Stein, E. S. Yolcu, D. L. Farkas, H. Shirwan, I. Yaniv, and N. Askenasy Fas Transduces Dual Apoptotic and Trophic Signals in Hematopoietic Progenitors Stem Cells, December 1, 2007; 25(12): 3194 - 3203. [Abstract] [Full Text] [PDF] M. Pearl-Yafe, E. S. Yolcu, J. Stein, O. Kaplan, I. Yaniv, H. Shirwan, and N. Askenasy Fas Ligand Enhances Hematopoietic Cell Engraftment Through Abrogation of Alloimmune Responses and Nonimmunogenic Interactions Stem Cells, June 1, 2007; 25(6): 1448 - 1455. [Abstract] [Full Text] [PDF] M. Buitenhuis, H. W. M. van Deutekom, L. P. Verhagen, A. Castor, S. E. W. Jacobsen, J.-W. J. Lammers, L. Koenderman, and P. J. Coffer Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2 Blood, June 1, 2005; 105(11): 4272 - 4281. [Abstract] [Full Text] [PDF]

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