C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.
Nat Cell Biol, 2013/4;15(4):385-94.
Ye M[1], Zhang H, Amabile G, Yang H, Staber PB, Zhang P, Levantini E, Alberich-Jordà M, Zhang J, Kawasaki A, Tenen DG
Affiliations
PMID: 23502316DOI: 10.1038/ncb2698
Impact factor: 28.213
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.
MeSH terms
Adult Stem Cells; Animals; Apoptosis; Biomarkers, Tumor; Blotting, Western; Bone Marrow Transplantation; CCAAT-Enhancer-Binding Proteins; Cell Cycle; Cell Differentiation; Cell Proliferation; Chromatin Immunoprecipitation; Fetal Stem Cells; Flow Cytometry; Gene Expression Profiling; Hematopoietic Stem Cells; Integrases; Luciferases; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction
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