View the Current Issue

Article

  • The EMBO Journal (2006) 25, 3398 - 3410
  • doi:10.1038/sj.emboj.7601199

Published online: 6 July 2006

Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPalpha

Yumi Fukuchi1, Fumi Shibata1,a, Miyuki Ito2,a, Yuko Goto-Koshino1, Yusuke Sotomaru3, Mamoru Ito3, Toshio Kitamura1 and Hideaki Nakajima2

  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

Correspondence to:

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

aThese authors contributed equally to this work

Received 20 September 2005; Accepted 29 May 2006

CCAAT/enhancer-binding protein (C/EBP) alpha is a critical regulator for early myeloid differentiation. Although C/EBPalpha has been shown to convert B cells into myeloid lineage, precise roles of C/EBPalpha in various hematopoietic progenitors and stem cells still remain obscure. To examine the consequence of C/EBPalpha 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/EBPalpha. 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/EBPalpha, and the conversion occurred clonally through biphenotypic intermediate cells. Moreover, in vivo activation of C/EBPalpha 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/EBPalpha can activate the latent myeloid differentiation program of MEP and CLP and shows that its global activation affects multilineage homeostasis in vivo.

  • Keywords:

    • CCAAT/enhancer-binding protein alpha,
    • C/EBPalpha,
    • hematopoietic progenitors,
    • plasticity,
    • transgenic mice