Posttranscriptional regulation of c-Myc expression in adult murine HSCs during homeostasis and interferon-α-induced stress response

Academic Article

Abstract

  • Previous studies have established pivotal roles for c-Myc and its homolog N-Myc in hematopoietic stem cell (HSC) maintenance and niche-dependent differentiation. However, it remains largely unclear how c-Myc expression is regulated in this context. Here, we show that HSCs and more committed progenitors express similar levels of c-myc transcripts. Using knock-in mice expressing a functional enhanced green fluorescent protein-c-Myc fusion protein under control of the endogenous c-myc locus, c-Myc protein levels were assessed. Although HSCs express low levels of c-Myc protein, its expression increases steadily during progenitor differentiation. Thus, mRNA and protein expression patterns differ significantly in stem/progenitor cells, suggesting that c-Myc expression is largely controlled posttranscriptionally. Moreover, interferon-α exposure, which activates dormant HSCs, strongly induces c-Myc expression at the protein level but not at the transcript level. This posttranscriptional mechanism of c-Myc regulation provides the blood system with a rapid way to adjust c-Myc expression according to demand during hematopoietic stress. © 2014 by The American Society of Hematology.
  • Authors

    Published In

  • Blood  Journal
  • Digital Object Identifier (doi)

    Author List

  • Ehninger A; Boch T; Uckelmann H; Essers MA; Müdder K; Sleckman BP; Trumpp A
  • Start Page

  • 3909
  • End Page

  • 3913
  • Volume

  • 123
  • Issue

  • 25