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Muscle injury causes long-term changes in stem-cell DNA methylation

Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation....

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Autores principales: Falick Michaeli, Tal, Sabag, Ofra, Fok, Rimma, Azria, Batia, Monin, Jonathan, Nevo, Yuval, Gielchinsky, Yuval, Berman, Benjamin P., Cedar, Howard, Bergman, Yehudit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907067/
https://www.ncbi.nlm.nih.gov/pubmed/36534800
http://dx.doi.org/10.1073/pnas.2212306119
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author Falick Michaeli, Tal
Sabag, Ofra
Fok, Rimma
Azria, Batia
Monin, Jonathan
Nevo, Yuval
Gielchinsky, Yuval
Berman, Benjamin P.
Cedar, Howard
Bergman, Yehudit
author_facet Falick Michaeli, Tal
Sabag, Ofra
Fok, Rimma
Azria, Batia
Monin, Jonathan
Nevo, Yuval
Gielchinsky, Yuval
Berman, Benjamin P.
Cedar, Howard
Bergman, Yehudit
author_sort Falick Michaeli, Tal
collection PubMed
description Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These de- and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis and are necessary for activation and regeneration. Local injury of one muscle elicits an almost identical epigenetic change in satellite cells from other muscles in the body, in a process mediated by circulating factors. Furthermore, this same methylation state is also generated in muscle stem cells (MuSCs) of female animals following pregnancy, even in the absence of any injury. Unlike the activation-induced expression changes, which are transient, the induced methylation profile is stably maintained in resident MuSCs and thus represents a molecular memory of previous physiological events that is probably programmed to provide a mechanism for long-term adaptation.
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spelling pubmed-99070672023-06-19 Muscle injury causes long-term changes in stem-cell DNA methylation Falick Michaeli, Tal Sabag, Ofra Fok, Rimma Azria, Batia Monin, Jonathan Nevo, Yuval Gielchinsky, Yuval Berman, Benjamin P. Cedar, Howard Bergman, Yehudit Proc Natl Acad Sci U S A Biological Sciences Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These de- and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis and are necessary for activation and regeneration. Local injury of one muscle elicits an almost identical epigenetic change in satellite cells from other muscles in the body, in a process mediated by circulating factors. Furthermore, this same methylation state is also generated in muscle stem cells (MuSCs) of female animals following pregnancy, even in the absence of any injury. Unlike the activation-induced expression changes, which are transient, the induced methylation profile is stably maintained in resident MuSCs and thus represents a molecular memory of previous physiological events that is probably programmed to provide a mechanism for long-term adaptation. National Academy of Sciences 2022-12-19 2022-12-27 /pmc/articles/PMC9907067/ /pubmed/36534800 http://dx.doi.org/10.1073/pnas.2212306119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Falick Michaeli, Tal
Sabag, Ofra
Fok, Rimma
Azria, Batia
Monin, Jonathan
Nevo, Yuval
Gielchinsky, Yuval
Berman, Benjamin P.
Cedar, Howard
Bergman, Yehudit
Muscle injury causes long-term changes in stem-cell DNA methylation
title Muscle injury causes long-term changes in stem-cell DNA methylation
title_full Muscle injury causes long-term changes in stem-cell DNA methylation
title_fullStr Muscle injury causes long-term changes in stem-cell DNA methylation
title_full_unstemmed Muscle injury causes long-term changes in stem-cell DNA methylation
title_short Muscle injury causes long-term changes in stem-cell DNA methylation
title_sort muscle injury causes long-term changes in stem-cell dna methylation
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907067/
https://www.ncbi.nlm.nih.gov/pubmed/36534800
http://dx.doi.org/10.1073/pnas.2212306119
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