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Blood, 1 July 2006, Vol. 108, No. 1, pp. 123-133. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-11-4458. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-11-4458v1 108/1/123    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Liu, Y. Articles by Socolovsky, M. Search for Related Content PubMed PubMed Citation Articles by Liu, Y. Articles by Socolovsky, M. Related Collections Hematopoiesis and Stem Cells Red Cells Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo Ying Liu, Ramona Pop, Cameron Sadegh, Carlo Brugnara, Volker H. Haase, and Merav Socolovsky From the Department of Pediatrics and Department of Cancer Biology, University of Massachusetts Medical School, Worcester; Department of Biology, Massachusetts Institute of Technology, Cambridge; Department of Laboratory Medicine, Children's Hospital, Harvard Medical School, Boston, MA; and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia. Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71HIGHfscHIGH early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and -thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo. (Blood. 2006;108:123-133) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. L. Chen, T. D. Logan, M. L. Hochberg, S. G. Shelat, X. Yu, G. E. Wilding, W. Tan, G. C. Kujoth, T. A. Prolla, M. A. Selak, et al. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction Blood, November 5, 2009; 114(19): 4045 - 4053. [Abstract] [Full Text] [PDF] M. T. Norton, K. A. Fortner, P. 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Clurman Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo Genes & Dev., June 15, 2008; 22(12): 1677 - 1689. [Abstract] [Full Text] [PDF] A. A. Lamikanra, D. Brown, A. Potocnik, C. Casals-Pascual, J. Langhorne, and D. J. Roberts Malarial anemia: of mice and men Blood, July 1, 2007; 110(1): 18 - 28. [Abstract] [Full Text] [PDF] P. Rimmele, O. Kosmider, P. Mayeux, F. Moreau-Gachelin, and C. Guillouf Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation Blood, April 1, 2007; 109(7): 3007 - 3014. [Abstract] [Full Text] [PDF]

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