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ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.

Knudsen, Kasper Jermiin; Rehn, Matilda; Hasemann, Marie Sigurd; Rapin, Nicolas; Bagger, Frederik Otzen; Ohlsson, Ewa; Willer, Anton; Frank, Anne-Katrine; Søndergaard, Elisabeth and Jendholm, Johan, et al. (2015) In Genes & Development 29(18). p.1915-1929
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... (More)
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. (Less)
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Genes & Development
volume
29
issue
18
pages
1915 - 1929
publisher
Cold Spring Harbor Laboratory Press
external identifiers
  • pmid:26385962
  • wos:000361749200004
  • scopus:84941962226
ISSN
1549-5477
DOI
10.1101/gad.268409.115
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English
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0b06b60c-a5b0-4587-8ef0-dfd1631e0814 (old id 8035847)
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http://www.ncbi.nlm.nih.gov/pubmed/26385962?dopt=Abstract
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2015-10-03 18:41:37
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@article{0b06b60c-a5b0-4587-8ef0-dfd1631e0814,
  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.},
  author       = {Knudsen, Kasper Jermiin and Rehn, Matilda and Hasemann, Marie Sigurd and Rapin, Nicolas and Bagger, Frederik Otzen and Ohlsson, Ewa and Willer, Anton and Frank, Anne-Katrine and Søndergaard, Elisabeth and Jendholm, Johan and Thorén, Lina and Lee, Julie and Rak, Justyna and Theilgaard-Moench, Kim and Porse, Bo Torben},
  issn         = {1549-5477},
  language     = {eng},
  number       = {18},
  pages        = {1915--1929},
  publisher    = {Cold Spring Harbor Laboratory Press},
  series       = {Genes & Development},
  title        = {ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.},
  url          = {http://dx.doi.org/10.1101/gad.268409.115},
  volume       = {29},
  year         = {2015},
}