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dc.contributor.authorFoudi, Adlenen_US
dc.contributor.authorKramer, Daniel J.en_US
dc.contributor.authorQin, Jinzhongen_US
dc.contributor.authorYe, Deniseen_US
dc.contributor.authorBehlich, Anna-Sophieen_US
dc.contributor.authorMordecai, Scotten_US
dc.contributor.authorPreffer, Frederic I.en_US
dc.contributor.authorAmzallag, Arnauden_US
dc.contributor.authorRamaswamy, Sridharen_US
dc.contributor.authorHochedlinger, Konraden_US
dc.contributor.authorOrkin, Stuart H.en_US
dc.contributor.authorHock, Hannoen_US
dc.date.accessioned2014-12-02T21:27:00Z
dc.date.issued2014en_US
dc.identifier.citationFoudi, A., D. J. Kramer, J. Qin, D. Ye, A. Behlich, S. Mordecai, F. I. Preffer, et al. 2014. “Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation.” The Journal of Experimental Medicine 211 (5): 909-927. doi:10.1084/jem.20131065. http://dx.doi.org/10.1084/jem.20131065.en
dc.identifier.issn0022-1007en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454621
dc.description.abstractThe zinc finger transcriptional repressor Gfi-1b is essential for erythroid and megakaryocytic development in the embryo. Its roles in the maintenance of bone marrow erythropoiesis and thrombopoiesis have not been defined. We investigated Gfi-1b’s adult functions using a loxP-flanked Gfi-1b allele in combination with a novel doxycycline-inducible Cre transgene that efficiently mediates recombination in the bone marrow. We reveal strict, lineage-intrinsic requirements for continuous adult Gfi-1b expression at two distinct critical stages of erythropoiesis and megakaryopoiesis. Induced disruption of Gfi-1b was lethal within 3 wk with severely reduced hemoglobin levels and platelet counts. The erythroid lineage was arrested early in bipotential progenitors, which did not give rise to mature erythroid cells in vitro or in vivo. Yet Gfi-1b−/− progenitors had initiated the erythroid program as they expressed many lineage-restricted genes, including Klf1/Eklf and Erythropoietin receptor. In contrast, the megakaryocytic lineage developed beyond the progenitor stage in Gfi-1b’s absence and was arrested at the promegakaryocyte stage, after nuclear polyploidization, but before cytoplasmic maturation. Genome-wide analyses revealed that Gfi-1b directly regulates a wide spectrum of megakaryocytic and erythroid genes, predominantly repressing their expression. Together our study establishes Gfi-1b as a master transcriptional repressor of adult erythropoiesis and thrombopoiesis.en
dc.language.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1084/jem.20131065en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010908/pdf/en
dash.licenseLAAen_US
dc.titleDistinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Experimental Medicineen
dash.depositing.authorKramer, Daniel J.en_US
dc.date.available2014-12-02T21:27:00Z
dc.identifier.doi10.1084/jem.20131065*
dash.authorsorderedfalse
dash.contributor.affiliatedKramer, Danny
dash.contributor.affiliatedAmzallag, Arnaud
dash.contributor.affiliatedRamaswamy, Sridhar
dash.contributor.affiliatedPreffer, Frederic
dash.contributor.affiliatedOrkin, Stuart
dash.contributor.affiliatedHochedlinger, Konrad
dash.contributor.affiliatedHock, Hanno


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