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

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

Authors :
Ye M
Zhang H
Amabile G
Yang H
Staber PB
Zhang P
Levantini E
Alberich-Jordà M
Zhang J
Kawasaki A
Tenen DG
Source :
Nature cell biology [Nat Cell Biol] 2013 Apr; Vol. 15 (4), pp. 385-94. Date of Electronic Publication: 2013 Mar 17.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1476-4679
Volume :
15
Issue :
4
Database :
MEDLINE
Journal :
Nature cell biology
Publication Type :
Academic Journal
Accession number :
23502316
Full Text :
https://doi.org/10.1038/ncb2698