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Prepublished online as a Blood First Edition Paper on August 29, 2002; DOI 10.1182/blood-2002-06-1918. This Article Full Text (PDF) All Versions of this Article: 2002-06-1918v1 101/2/517    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 Ito, C. Y Articles by Stanford, W. L Search for Related Content PubMed PubMed Citation Articles by Ito, C. Y Articles by Stanford, W. L Social Bookmarking                   What's this? Submitted June 28, 2002 Accepted August 14, 2002 Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A null mice Caryn Y Ito, Carol Y J Li, Alan Bernstein, John E Dick, and William L Stanford* Programme in Cancer/Blood, Hospital for Sick Children, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada Programme in Development and Fetal Health, Samuel Lunenfeld Research Institute, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Toronto, ON, Canada; Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada Programme in Cancer/Blood, Hospital for Sick Children, Toronto, ON, Canada; Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada * Corresponding author; email: william.stanford{at}utoronto.ca. Despite its wide use as a marker for hematopoietic stem cells (HSCs), the function of Sca-1 (a.k.a., Ly-6A) in hematopoiesis remains poorly defined. We have previously established that Sca-1-/- T cells develop normally, although they are hyper-responsive to antigen. Here, we report detailed analysis of hematopoiesis in Sca-1 deficient animals. The differentiation potential of Sca-1 null bone marrow was determined from the most mature precursors (colony forming unit-culture, CFU-C) to less committed progenitors (CFU-Spleen, CFU-S) to long term repopulating HSCs. Sca-1 null mice are mildly thrombocytopenic with a concomitant decrease in megakaryocytes and their precursors. Bone marrow cells derived from Sca-1-/- mice also have decreased multipotential CFU-granulocyte, erythroid, macrophage, and megakaryocyte (CFU-GEMM) and CFU-S progenitor activity. Competitive repopulation assays demonstrated that Sca-1-/- HSCs are at a competitive disadvantage compared to wild-type HSCs. To further analyze the potential of Sca-1-/- HSCs, serial transplants were performed. While secondary repopulations using wild type bone marrow completely repopulated Sca-1-/- mice, Sca-1-/- bone marrow failed to rescue one-third of lethally-irradiated wild type mice receiving secondary bone marrow transplants from irradiation-induced anemia and contributed poorly to the surviving transplant recipients. These data strongly suggest that Sca-1 is required for regulating HSC self-renewal and the development of committed progenitor cells, megakaryocytes and platelets. Thus, our studies conclusively demonstrate that Sca-1, in addition to being a marker of HSCs, regulates the developmental program of HSCs and specific progenitor populations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hidestrand, S. Richards-Malcolm, C. M. Gurley, G. Nolen, B. Grimes, A. Waterstrat, G. V. Zant, and C. A. 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