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ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.
- Source :
-
Genes & development [Genes Dev] 2015 Sep 15; Vol. 29 (18), pp. 1915-29. - Publication Year :
- 2015
-
Abstract
- The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation. Specifically, loss of Erg accelerates HSC differentiation by >20-fold, thus leading to rapid depletion of immunophenotypic and functional HSCs. Molecularly, we could demonstrate that ERG, in addition to promoting the expression of HSC self-renewal genes, also represses a group of MYC targets, thereby explaining why Erg loss closely mimics Myc overexpression. Consistently, the BET domain inhibitor CPI-203, known to repress Myc expression, confers a partial phenotypic rescue. In summary, ERG plays a critical role in coordinating the balance between self-renewal and differentiation of HSCs.<br /> (© 2015 Knudsen et al.; Published by Cold Spring Harbor Laboratory Press.)
- Subjects :
- Animals
Bone Marrow Cells physiology
Cell Adhesion genetics
Cell Movement genetics
Cell Transformation, Neoplastic genetics
Cells, Cultured
Gene Deletion
Mice
Oncogene Proteins genetics
Transcription Factors genetics
Transcriptional Regulator ERG
Cell Differentiation genetics
Hematopoietic Stem Cells cytology
Oncogene Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1549-5477
- Volume :
- 29
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 26385962
- Full Text :
- https://doi.org/10.1101/gad.268409.115