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

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Author

  • 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
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Summary, in English

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.

Publishing year

2008

Language

English

Pages

584-594

Publication/Series

Cell Stem Cell

Volume

2

Issue

6

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1934-5909