期刊
NATURE CELL BIOLOGY
卷 15, 期 4, 页码 385-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2698
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资金
- National Institutes of Health [HL 56745]
- Harvard Stem Cell Institute [DP-0086-10-00]
- Collegio Ghislieri Fellowship Program
- FAMRI YCSA
- CIA
- Austrian Research Foundation
- European Union
- Singapore Ministry of Health's National Medical Research Council under Singapore Translational Research (STaR) Investigator Award
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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