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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.
- 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.
- Subjects :
- Adult Stem Cells physiology
Animals
Apoptosis
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Blotting, Western
Bone Marrow Transplantation
Cell Cycle
Chromatin Immunoprecipitation
Fetal Stem Cells physiology
Flow Cytometry
Gene Expression Profiling
Hematopoietic Stem Cells physiology
Integrases metabolism
Luciferases metabolism
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins c-myc genetics
Proto-Oncogene Proteins c-myc metabolism
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Adult Stem Cells cytology
CCAAT-Enhancer-Binding Proteins physiology
Cell Differentiation
Cell Proliferation
Fetal Stem Cells cytology
Hematopoietic Stem Cells cytology
Subjects
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