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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3398-3410
Number of pages13
JournalEMBO Journal
Volume25
Issue number14
DOIs
Publication statusPublished - 2006 Jul 26

Keywords

  • C/EBPα
  • CCAAT/enhancer-binding protein α
  • Hematopoietic progenitors
  • Plasticity
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Fukuchi, Y., Shibata, F., Ito, M., Goto-Koshino, Y., Sotomaru, Y., Ito, M., Kitamura, T., & Nakajima, H. (2006). Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPα. EMBO Journal, 25(14), 3398-3410. https://doi.org/10.1038/sj.emboj.7601199