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

Yumi Fukuchi, Fumi Shibata, Miyuki Ito, Yuko Goto-Koshino, Yusuke Sotomaru, Mamoru Ito, Toshio Kitamura, Hideaki Nakajima

研究成果: Article査読

48 被引用数 (Scopus)

抄録

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

本文言語English
ページ(範囲)3398-3410
ページ数13
ジャーナルEMBO Journal
25
14
DOI
出版ステータスPublished - 2006 7 26

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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