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Nat Cell Biol. 2013 Apr;15(4):385-94. doi: 10.1038/ncb2698. Epub 2013 Mar 17.

C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.

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  • 1Harvard Stem Cell Institute, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.

Abstract

In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver haematopoietic stem cells (HSCs). However, its function in adult HSCs has remained unknown. Here, using an inducible knockout model we found that C/EBPa-deficient adult HSCs underwent a pronounced increase in number with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa-deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover, we observed that age-specific Cebpa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically we identified N-Myc as a downstream target of C/EBPa, and loss of C/EBPa resulted in de-repression of N-Myc. Our data establish C/EBPa as a central determinant in the switch from fetal to adult HSCs.

PMID:
23502316
[PubMed - indexed for MEDLINE]
PMCID:
PMC3781213
Free PMC Article
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