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

In English

Författare

  • Kasper Jermiin Knudsen
  • Matilda Rehn
  • Marie Sigurd Hasemann
  • Nicolas Rapin
  • Frederik Otzen Bagger
  • Ewa Ohlsson
  • Anton Willer
  • Anne-Katrine Frank
  • Elisabeth Søndergaard
  • Johan Jendholm
  • Lina Thorén
  • Julie Lee
  • Justyna Rak
  • Kim Theilgaard-Moench
  • Bo Torben Porse
Visa allt

Summary, in English

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.

Publiceringsår

2015

Språk

Engelska

Sidor

1915-1929

Publikation/Tidskrift/Serie

Genes & Development

Volym

29

Issue

18

Dokumenttyp

Artikel i tidskrift

Förlag

Cold Spring Harbor Laboratory Press (CSHL)

Ämne

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1549-5477