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

First Author  Ye M Year  2013
Journal  Nat Cell Biol Volume  15
Issue  4 Pages  385-94
PubMed ID  23502316 Mgi Jnum  J:197635
Mgi Id  MGI:5494206 Doi  10.1038/ncb2698
Citation  Ye M, et al. (2013) C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nat Cell Biol 15(4):385-94
abstractText  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.
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