Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3

Research output: Contribution to journalArticle

Abstract

Limited responsiveness to inflammatory cytokines is a feature of adult hematopoietic stem cells and contributes to the relative quiescence and durability of the stem cell population in vivo. Here we report that the executioner Caspase, Caspase-3, unexpectedly participates in that process. Mice deficient in Caspase-3 had increased numbers of immunophenotypic long-term repopulating stem cells in association with multiple functional changes, most prominently cell cycling. Though these changes were cell autonomous, they reflected altered activation by exogenous signals. Caspase-3(-/-) cells exhibited cell type-specific changes in phosphorylated members of the Ras-Raf-MEK-ERK pathway in response to specific cytokines, while notably, members of other pathways, such as pSTAT3, pSTAT5, pAKT, pp38 MAPK, pSmad2, and pSmad3, were unaffected. Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli.

Details

Authors
  • Viktor Janzen
  • Heather E Fleming
  • Tamara Riedt
  • Göran Karlsson
  • Matthew J Riese
  • Cristina Lo Celso
  • Griffin Reynolds
  • Craig D Milne
  • Christopher J Paige
  • Stefan Karlsson
  • Minna Woo
  • David T Scadden
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology
Original languageEnglish
Pages (from-to)584-594
JournalCell Stem Cell
Volume2
Issue number6
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes