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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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes & Development
volume
29
issue
18
pages
1915 - 1929
publisher
Cold Spring Harbor Laboratory Press (CSHL)
external identifiers
  • pmid:26385962
  • wos:000361749200004
  • scopus:84941962226
  • pmid:26385962
ISSN
1549-5477
DOI
10.1101/gad.268409.115
language
English
LU publication?
yes
id
0b06b60c-a5b0-4587-8ef0-dfd1631e0814 (old id 8035847)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26385962?dopt=Abstract
date added to LUP
2016-04-01 10:03:29
date last changed
2022-08-12 08:17:35
@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 (CSHL)}},
  series       = {{Genes & Development}},
  title        = {{ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.}},
  url          = {{https://lup.lub.lu.se/search/files/8198368/Knudsen_et_al.pdf}},
  doi          = {{10.1101/gad.268409.115}},
  volume       = {{29}},
  year         = {{2015}},
}