{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:13:31Z","timestamp":1792721611916,"version":"4.5.0"},"reference-count":43,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,15]]},"abstract":"<jats:p>Despite its wide use as a marker for hematopoietic stem cells (HSCs), the function of stem cell antigen\u20131 (Sca-1) (also known as lymphocyte activation protein\u20136A [Ly-6A]) in hematopoiesis remains poorly defined. We have previously established that Sca-1\u2212\/\u2212T cells develop normally, although they are hyperresponsive to antigen. Here, we report detailed analysis of hematopoiesis in Sca-1\u2013deficient animals. The differentiation potential of Sca-1\u2013null bone marrow was determined from examination of the most mature precursors (culture colony-forming units [CFU-Cs]) to less committed progenitors (spleen CFUs [CFU-Ss]) to long-term repopulating HSCs. Sca-1\u2013null mice are mildly thrombocytopenic with a concomitant decrease in megakaryocytes and their precursors. Bone marrow cells derived fromSca-1\u2212\/\u2212 mice also have decreased multipotential granulocyte, erythroid, macrophage, and megakaryocyte CFU (GEMM-CFU) and CFU-S progenitor activity. Competitive repopulation assays demonstrated that Sca-1\u2212\/\u2212HSCs are at a competitive disadvantage compared with wild-type HSCs. To further analyze the potential of Sca-1\u2212\/\u2212HSCs, serial transplantations were performed. While secondary repopulations using wild-type bone marrow completely repopulatedSca-1\u2212\/\u2212mice, Sca-1\u2212\/\u2212bone 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.<\/jats:p>","DOI":"10.1182\/blood-2002-06-1918","type":"journal-article","created":{"date-parts":[[2002,12,31]],"date-time":"2002-12-31T00:55:15Z","timestamp":1041296115000},"page":"517-523","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":166,"title":["Hematopoietic stem cell and progenitor defects in Sca-1\/Ly-6A\u2013null mice"],"prefix":"10.1182","volume":"101","author":[{"given":"Caryn Y.","family":"Ito","sequence":"first","affiliation":[{"name":"From the Programme in Cancer\/Blood, Hospital for Sick Children, Toronto, ON, Canada; the Programme in Development and Fetal Health and the Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics and the Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Y. J.","family":"Li","sequence":"additional","affiliation":[{"name":"From the Programme in Cancer\/Blood, Hospital for Sick Children, Toronto, ON, Canada; the Programme in Development and Fetal Health and the Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics and the Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Bernstein","sequence":"additional","affiliation":[{"name":"From the Programme in Cancer\/Blood, Hospital for Sick Children, Toronto, ON, Canada; the Programme in Development and Fetal Health and the Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics and the Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Dick","sequence":"additional","affiliation":[{"name":"From the Programme in Cancer\/Blood, Hospital for Sick Children, Toronto, ON, Canada; the Programme in Development and Fetal Health and the Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics and the Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Stanford","sequence":"additional","affiliation":[{"name":"From the Programme in Cancer\/Blood, Hospital for Sick Children, Toronto, ON, Canada; the Programme in Development and Fetal Health and the Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and 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