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We now show that conditional deletion of ZBP-89 in adult mouse hematopoietic stem\/progenitor cells (HSPC) causes anemia and thrombocytopenia that are transient in the steady state, but readily uncovered following chemically induced erythro\/megakaryopoietic stress. Unexpectedly, stress induced by bone marrow transplantation of ZBP89\u2212\/\u2212 HSPC also resulted in a myeloid-to-B lymphoid lineage switch in bone marrow recipients. The erythroid and myeloid\/B lymphoid lineage anomalies in ZBP89\u2212\/\u2212 HSPC are reproduced in vitro in the ZBP-89-silenced multipotent hematopoietic cell line FDCP-Mix A4, and are associated with the upregulation of PU.1 and downregulation of SCL\/Tal1 and GATA-1 in ZBP89-deficient cells. Chromatin immunoprecipitation and luciferase reporter assays show that ZBP-89 is a direct repressor of PU.1 and activator of SCL\/Tal1 and GATA-1. These data identify an important role for ZBP-89 in regulating stress hematopoiesis in adult mouse bone marrow. Stem Cells \u00a02014;32:791\u2013801<\/jats:p>","DOI":"10.1002\/stem.1598","type":"journal-article","created":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T09:27:03Z","timestamp":1383902823000},"page":"791-801","source":"Crossref","is-referenced-by-count":9,"title":["Stress Hematopoiesis Is Regulated by the Kr\u00fcppel-Like Transcription Factor ZBP-89"],"prefix":"10.1093","volume":"32","author":[{"given":"Xiangen","family":"Li","sequence":"first","affiliation":[{"name":"Leukocyte Biology & Inflammation Program, Division of Nephrology Massachusetts General Hospital, Charlestown, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael D.","family":"Romain","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongsu","family":"Park","sequence":"additional","affiliation":[{"name":"Center For Regenerative Medicine Massachusetts General Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Stem Cell Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T.","family":"Scadden","sequence":"additional","affiliation":[{"name":"Center For Regenerative Medicine Massachusetts General Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Stem Cell Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanita L.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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