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

Janzen, Viktor; Fleming, Heather E; Riedt, Tamara; Karlsson, Göran LU ; Riese, Matthew J; Lo Celso, Cristina; Reynolds, Griffin; Milne, Craig D; Paige, Christopher J and Karlsson, Stefan LU , et al. (2008) In Cell Stem Cell 2(6). p.584-594
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
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Cell Stem Cell
volume
2
issue
6
pages
584 - 594
publisher
Cell Press
external identifiers
  • wos:000256870000016
  • scopus:44349188910
ISSN
1934-5909
DOI
10.1016/j.stem.2008.03.012
language
English
LU publication?
yes
id
62334a90-e5af-4789-a176-2912ae7bd016 (old id 1191130)
date added to LUP
2008-09-08 11:38:08
date last changed
2017-10-01 03:55:58
@article{62334a90-e5af-4789-a176-2912ae7bd016,
  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.},
  author       = {Janzen, Viktor and Fleming, Heather E and Riedt, Tamara and Karlsson, Göran and Riese, Matthew J and Lo Celso, Cristina and Reynolds, Griffin and Milne, Craig D and Paige, Christopher J and Karlsson, Stefan and Woo, Minna and Scadden, David T},
  issn         = {1934-5909},
  language     = {eng},
  number       = {6},
  pages        = {584--594},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3},
  url          = {http://dx.doi.org/10.1016/j.stem.2008.03.012},
  volume       = {2},
  year         = {2008},
}