ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.
(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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https://lup.lub.lu.se/record/8035847
- author
- organization
- publishing date
- 2015
- 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}}, }