C/EBPa Controls Acquisition and Maintenance of Adult Haematopoietic Stem Cell Quiescence

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2013 Mar 19

PMID 23502316

Citations 85

Authors

Min Ye

Hong Zhang

Giovanni Amabile

Henry Yang

Philipp B Staber

Pu Zhang

Elena Levantini

Meritxell Alberich-Jorda

Junyan Zhang

Akira Kawasaki

Daniel G Tenen

Affiliations

Soon will be listed here.

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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