Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ye, M; Zhang, H; Amabile, G; Yang, H; Staber, PB; Zhang, P; Levantini, E; Alberich-Jorda, M; Zhang, JY; Kawasaki, A; Tenen, DG; .
C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.
Nat Cell Biol. 2013; 15(4):385-394
Doi: 10.1038/ncb2698
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- Co-Autor*innen der Med Uni Graz
- Staber Philipp
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- 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.
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