Ye, MinZhang, HongAmabile, GiovanniYang, HenryStaber, Philipp B.Zhang, PuLevantini, ElenaAlberich-Jordà, MeritxellZhang, JunyanKawasaki, AkiraTenen, Daniel2014-03-102013Ye, 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/ncb2698.1465-7392http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878939Summary 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.en-USTranscription factorC/EBPahematopoietic stem cellquiescenceproliferationN-MycJournal Article2014-03-1010.1038/ncb2698