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

Publikace na Ústřední knihovna |
2013

Tento text není v aktuálním jazyce dostupný. Zobrazuje se verze "en".Abstrakt

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.