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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1191130
- author
- 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. (More)
- Janzen, Viktor
; Fleming, Heather E
; Riedt, Tamara
; Karlsson, Göran
LU
; Riese, Matthew J
; Lo Celso, Cristina
; Reynolds, Griffin
; Milne, Craig D
; Paige, Christopher J
; Karlsson, Stefan
LU
; Woo, Minna
and Scadden, David T
(Less)
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- 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
- 2016-04-01 12:29:16
- date last changed
- 2022-03-29 01:35:24
@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}},
doi = {{10.1016/j.stem.2008.03.012}},
volume = {{2}},
year = {{2008}},
}