C/EBPa controls acquisition and maintenance of adult hematopoietic stem cell quiescence
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CitationYe, M., H. Zhang, G. Amabile, H. Yang, P. B. Staber, P. Zhang, E. Levantini, et al. 2013. “C/EBPa controls acquisition and maintenance of adult hematopoietic stem cell quiescence.” Nature cell biology 15 (4): 385-394. doi:10.1038/ncb2698. http://dx.doi.org/10.1038/ncb2698.
AbstractSummary In blood, transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver (FL) hematopoietic 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 expansion with enhanced proliferation, characteristics resembling FL HSCs. Consistently, transcription profiling of C/EBPa deficient HSCs revealed a gene expression programme similar to FL HSCs. Moreover we observed that age-specific C/EBPa expression correlated with its inhibitory effect on HSC cell cycle. Mechanistically we identified N-Myc as C/EBPa downstream target, 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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