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|Title:||C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence|
|Citation:||Ye, M., Zhang, H., Amabile, G., Yang, H., Staber, P.B., Zhang, P., Levantini, E., Alberich-Jordà, M., Zhang, J., Kawasaki, A., Tenen, D.G. (2013-04). C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nature Cell Biology 15 (4) : 385-394. ScholarBank@NUS Repository. https://doi.org/10.1038/ncb2698|
|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. © 2013 Macmillan Publishers Limited. All rights reserved.|
|Source Title:||Nature Cell Biology|
|Appears in Collections:||Staff Publications|
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