Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3
Författare
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.
Avdelning/ar
Publiceringsår
2008
Språk
Engelska
Sidor
584-594
Publikation/Tidskrift/Serie
Cell Stem Cell
Volym
2
Issue
6
Dokumenttyp
Artikel i tidskrift
Förlag
Cell Press
Ämne
- Cell Biology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1934-5909