ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification

Samir Taoudi, Thomas Bee, Adrienne Hilton, Kathy Knezevic, Julie Scott, Tracy A. Willson, Caitlin Collin, Tim Thomas, Anne K. Voss, Benjamin T. Kile, Warren S. Alexander, John E. Pimanda, Douglas J. Hilton

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62 Citations (Scopus)

Abstract

Although many genes are known to be critical for early hematopoiesis in the embryo, it remains unclear whether distinct regulatory pathways exist to control hematopoietic specification versus hematopoietic stem cell (HSC) emergence and function. Due to their interaction with key regulators of hematopoietic commitment, particular interest has focused on the role of the ETS family of transcription factors; of these, ERG is predicted to play an important role in the initiation of hematopoiesis, yet we do not know if or when ERG is required. Using in vitro and in vivo models of hematopoiesis and HSC development, we provide strong evidence that ERG is at the center of a distinct regulatory program that is not required for hematopoietic specification or differentiation but is critical for HSC maintenance during embryonic development. We show that, from the fetal period, ERG acts as a direct upstream regulator of Gata2 and Runx1 gene activity. Without ERG, physiological HSC maintenance fails, leading to the rapid exhaustion of definitive hematopoiesis.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalGenes & Development
Volume25
Issue number3
DOIs
Publication statusPublished - Feb 2011
Externally publishedYes

Keywords

  • ERG
  • ETS family transcription factors
  • Gata2
  • Hematopoietic development
  • Hematopoietic stem cells
  • Runx1
  • Self-renewal

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