Activation of CCAAT/enhancer-binding protein α or PU.1 in hematopoietic stem cells leads to their reduced self-renewal and proliferation

Yumi Fukuchi, Miyuki Ito, Fumi Shibata, Toshio Kitamura, Hideaki Nakajima

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Previous studies using loss-of-function mutants revealed that CCAAT/enhancer-binding protein α (C/EBPα) and PU.1 are potential regulators for hematopoietic stem cells (HSCs). To gain further insight into the HSC regulation by C/EBPα or PU.1, we used transgenic mice expressing conditional forms of these transcription factors to examine whether their activation alone is sufficient for modulating HSC functions. The activation of C/EBPα or PU.1 in HSCs in vitro or in vivo led to their suppression of growth, decreased mixed colony formation, and impaired competitive repopulating activities because of their defective self-renewal. These effects were more prominently observed when C/EBPα was activated, and the differentiation capacity to megakaryocytic lineage was selectively impaired upon C/EBPα activation. Unexpectedly, the expression of Bmi-1 and HoxB4, well-known regulators for self-renewal of HSCs, was not affected by the activation of C/EBPα or PU.1, suggesting that they regulate HSC function through an as yet unknown mechanism. Our data suggest that the activation of C/EBPα or PU.1 is sufficient to repress stem cell capacities in HSCs, and their fine-tuned regulation is critical for HSC homeostasis.

Original languageEnglish
Pages (from-to)3172-3181
Number of pages10
JournalStem Cells
Volume26
Issue number12
DOIs
Publication statusPublished - 2008 Dec 1

Keywords

  • CCAAT/enhancer-binding protein α
  • Hematopoietic stem cell
  • PU.1
  • Self-renewal

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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