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| Subject Categories: Differentiation & Death | Immunology |
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| The EMBO Journal
(2006) 25, 3398–3410, doi:10.1038/sj.emboj.7601199 Published online 6 July 2006 |
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Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBP |
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| Yumi Fukuchi1, Fumi Shibata1, 4, Miyuki Ito2, 4, Yuko Goto-Koshino1, Yusuke Sotomaru3, Mamoru Ito3, Toshio Kitamura1 and Hideaki Nakajima2 |
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1 Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan 2 Center of Excellence, Institute of Medical Science, University of Tokyo, Tokyo, Japan 3 Central Institute for Experimental Animals, Kanagawa, Japan To whom correspondence should be addressed Hideaki Nakajima, Center of Excellence, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Tel.: +81 3 5449 5759; Fax: +81 3 5449 5453; E-mail: hnakajim@ims.u-tokyo.ac.jp 4 These authors contributed equally to this work Received 20 September 2005; Accepted 29 May 2006; Published online 6 July 2006. |
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| Abstract |
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| CCAAT/enhancer-binding protein (C/EBP) is a critical regulator for early myeloid differentiation. Although C/EBP has been shown to convert B cells into myeloid lineage, precise roles of C/EBP in various hematopoietic progenitors and stem cells still remain obscure. To examine the consequence of C/EBP activation in various progenitors and to address the underlying mechanism of lineage conversion in detail, we established transgenic mice expressing a conditional form of C/EBP. Using these mice, we show that megakaryocyte/erythroid progenitors (MEPs) and common lymphoid progenitors (CLPs) could be redirected to functional macrophages in vitro by a short-term activation of C/EBP, and the conversion occurred clonally through biphenotypic intermediate cells. Moreover, in vivo activation of C/EBP in mice led to the increase of mature granulocytes and myeloid progenitors with a concomitant decrease of hematopoietic stem cells and nonmyeloid progenitors. Our study reveals that C/EBP can activate the latent myeloid differentiation program of MEP and CLP and shows that its global activation affects multilineage homeostasis in vivo. |
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| Keywords: CCAAT/enhancer-binding protein , C/EBP, hematopoietic progenitors, plasticity, transgenic mice |
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