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Tytuł pozycji:

An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.

Tytuł:
An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling.
Autorzy:
Kann AP; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hung M; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Wang W; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nguyen J; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S3E1, Canada.
Gilbert PM; Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S3E1, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S3G5, Canada.
Wu Z; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Krauss RS; Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: .
Źródło:
Cell stem cell [Cell Stem Cell] 2022 Jun 02; Vol. 29 (6), pp. 933-947.e6. Date of Electronic Publication: 2022 May 20.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
Język:
English
Imprint Name(s):
Original Publication: Cambridge, MA : Cell Press
MeSH Terms:
Satellite Cells, Skeletal Muscle*/metabolism
rho GTP-Binding Proteins*/metabolism
Muscle Fibers, Skeletal/metabolism ; Muscle, Skeletal ; Myoblasts/metabolism ; Stem Cells/metabolism
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Grant Information:
R01 AR070231 United States AR NIAMS NIH HHS; T32 HD075735 United States HD NICHD NIH HHS
Contributed Indexing:
Keywords: GTPase; Rac1; Rho; cytoskeleton; mechanosignaling; muscle stem cell; quiescence; satellite cell; stem cell activation; stem cell niche
Substance Nomenclature:
EC 3.6.5.2 (rho GTP-Binding Proteins)
Entry Date(s):
Date Created: 20220521 Date Completed: 20220608 Latest Revision: 20230603
Update Code:
20240105
PubMed Central ID:
PMC9177759
DOI:
10.1016/j.stem.2022.04.016
PMID:
35597234
Czasopismo naukowe
Many tissues harbor quiescent stem cells that are activated upon injury, subsequently proliferating and differentiating to repair tissue damage. Mechanisms by which stem cells sense injury and transition from quiescence to activation, however, remain largely unknown. Resident skeletal muscle stem cells (MuSCs) are essential orchestrators of muscle regeneration and repair. Here, with a combination of in vivo and ex vivo approaches, we show that quiescent MuSCs have elaborate, Rac GTPase-promoted cytoplasmic projections that respond to injury via the upregulation of Rho/ROCK signaling, facilitating projection retraction and driving downstream activation events. These early events involve rapid cytoskeletal rearrangements and occur independently of exogenous growth factors. This mechanism is conserved across a broad range of MuSC activation models, including injury, disease, and genetic loss of quiescence. Our results redefine MuSC activation and present a central mechanism by which quiescent stem cells initiate responses to injury.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2022 Elsevier Inc. All rights reserved.)

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