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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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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.

OriginalsprogEngelsk
TidsskriftGenes & Development
Vol/bind29
Udgave nummer18
Sider (fra-til)1915-29
Antal sider15
ISSN0890-9369
DOI
StatusUdgivet - 15 sep. 2015

ID: 45654426