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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)1915-1929
JournalGenes & Development
Volume29
Issue number18
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes

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