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

Genes Dev. 2015 Sep 15;29(18):1915-29. doi: 10.1101/gad.268409.115.


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.

Keywords: CPI-203; ERG; MYC; differentiation; hematopoietic stem cell; self-renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • Cell Adhesion / genetics
  • Cell Differentiation / genetics*
  • Cell Movement / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cells, Cultured
  • Gene Deletion
  • Hematopoietic Stem Cells / cytology*
  • Mice
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Regulator ERG


  • ERG protein, mouse
  • Oncogene Proteins
  • Transcription Factors
  • Transcriptional Regulator ERG