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

46 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
Externally publishedYes

Fingerprint

CCAAT-Enhancer-Binding Proteins
Megakaryocyte-Erythroid Progenitor Cells
Lymphoid Progenitor Cells
Hematopoietic Stem Cells
Chemical activation
Stem cells
Granulocyte Precursor Cells
Macrophages
Transgenic Mice
Homeostasis
B-Lymphocytes
Cells

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Fukuchi, Y., Shibata, F., Ito, M., Goto-Koshino, Y., Sotomaru, Y., Ito, M., ... 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

Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPα. / Fukuchi, Yumi; Shibata, Fumi; Ito, Miyuki; Goto-Koshino, Yuko; Sotomaru, Yusuke; Ito, Mamoru; Kitamura, Toshio; Nakajima, Hideaki.

In: EMBO Journal, Vol. 25, No. 14, 26.07.2006, p. 3398-3410.

Research output: Contribution to journalArticle

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, vol. 25, no. 14, pp. 3398-3410. https://doi.org/10.1038/sj.emboj.7601199
Fukuchi Y, Shibata F, Ito M, Goto-Koshino Y, Sotomaru Y, Ito M et al. Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPα. EMBO Journal. 2006 Jul 26;25(14):3398-3410. https://doi.org/10.1038/sj.emboj.7601199
Fukuchi, Yumi ; Shibata, Fumi ; Ito, Miyuki ; Goto-Koshino, Yuko ; Sotomaru, Yusuke ; Ito, Mamoru ; Kitamura, Toshio ; Nakajima, Hideaki. / Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPα. In: EMBO Journal. 2006 ; Vol. 25, No. 14. pp. 3398-3410.
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