CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration

Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We sh...

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Autores: Sreenivasan, Krishnamoorthy, Rodríguez de la Rosa, Alejandra, Kim, Johnny, Mesquita, Diana, Segalés Dalmau, Jessica, Gómez del Arco, Pablo, Espejo, Isabel, Ianni, Alessandro, Di Croce, Luciano, Relaix, Frederic, Redondo, Juan Miguel, Braun, Thomas, Serrano Sánchez, Antonio L., Perdiguero, Eusebio, 1968-, Muñoz Cánoves, Pura, 1962-
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2021
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/48691
Acesso em linha:http://hdl.handle.net/10230/48691
http://dx.doi.org/10.1016/j.stemcr.2021.07.022
Access Level:Acceso aberto
Palavra-chave:Chd4
NuRD
Lineage maintenance
Muscle stem cell
Regeneration
Satellite cells
Skeletal muscle
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spelling CHD4 ensures stem cell lineage fidelity during skeletal muscle regenerationSreenivasan, KrishnamoorthyRodríguez de la Rosa, AlejandraKim, JohnnyMesquita, DianaSegalés Dalmau, JessicaGómez del Arco, PabloEspejo, IsabelIanni, AlessandroDi Croce, LucianoRelaix, FredericRedondo, Juan MiguelBraun, ThomasSerrano Sánchez, Antonio L.Perdiguero, Eusebio, 1968-Muñoz Cánoves, Pura, 1962-Chd4NuRDLineage maintenanceMuscle stem cellRegenerationSatellite cellsSkeletal muscleRegeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We show that conditional deletion of the Chd4 gene in satellite cells results in failure to regenerate muscle after injury. This defect is principally associated with increased stem cell plasticity and lineage infidelity during the expansion of satellite cells, caused by de-repression of non-muscle-cell lineage genes in the absence of Chd4. Thus, CHD4 ensures that a transcriptional program that safeguards satellite cell identity during muscle regeneration is maintained. Given the therapeutic potential of muscle stem cells in diverse neuromuscular pathologies, CHD4 constitutes an attractive target for satellite cell-based therapies.The authors acknowledge funding from MINECO -Spain (grant no. RTI2018-096068 ), ERC - AdG-741966 , LaCaixa-HEALTH- HR17-00040 , MWRF, MDA, UPGRADE- H2020-825825 , AFM , and DPP -Spain to P.M.C. P.G.-d.A. was supported by MINECO-Spain (grant no. SAF2016-77816-P ); French ANR Labex REVIVE (grant no. ANR-10-LABX-73 ) to F.R. A.R. was supported by a DCEXS -UPF, BIST Fellowship. Fundació la Marató de TV3 supported A.L.S. (grant no. 202033 ) and P.M.C. (grant no. 202021 ) and the María-de-Maeztu-Program for Units of Excellence to UPF (grant no. MDM-2014-0370 ) and the Severo-Ochoa-Program for Centers of Excellence to CNIC (grant no. SEV-2015-0505 ).Elsevier202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/48691http://dx.doi.org/10.1016/j.stemcr.2021.07.022reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésStem Cell Reports. 2021;16(9):2089-98info:eu-repo/grantAgreement/EC/H2020/741966info:eu-repo/grantAgreement/EC/H2020/825825info:eu-repo/grantAgreement/ES/1PE/SAF2016-77816-Pinfo:eu-repo/grantAgreement/ES/2PE/RTI2018-096068© 2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/486912026-05-29T05:05:01Z
dc.title.none.fl_str_mv CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
title CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
spellingShingle CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
Sreenivasan, Krishnamoorthy
Chd4
NuRD
Lineage maintenance
Muscle stem cell
Regeneration
Satellite cells
Skeletal muscle
title_short CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
title_full CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
title_fullStr CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
title_full_unstemmed CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
title_sort CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
dc.creator.none.fl_str_mv Sreenivasan, Krishnamoorthy
Rodríguez de la Rosa, Alejandra
Kim, Johnny
Mesquita, Diana
Segalés Dalmau, Jessica
Gómez del Arco, Pablo
Espejo, Isabel
Ianni, Alessandro
Di Croce, Luciano
Relaix, Frederic
Redondo, Juan Miguel
Braun, Thomas
Serrano Sánchez, Antonio L.
Perdiguero, Eusebio, 1968-
Muñoz Cánoves, Pura, 1962-
author Sreenivasan, Krishnamoorthy
author_facet Sreenivasan, Krishnamoorthy
Rodríguez de la Rosa, Alejandra
Kim, Johnny
Mesquita, Diana
Segalés Dalmau, Jessica
Gómez del Arco, Pablo
Espejo, Isabel
Ianni, Alessandro
Di Croce, Luciano
Relaix, Frederic
Redondo, Juan Miguel
Braun, Thomas
Serrano Sánchez, Antonio L.
Perdiguero, Eusebio, 1968-
Muñoz Cánoves, Pura, 1962-
author_role author
author2 Rodríguez de la Rosa, Alejandra
Kim, Johnny
Mesquita, Diana
Segalés Dalmau, Jessica
Gómez del Arco, Pablo
Espejo, Isabel
Ianni, Alessandro
Di Croce, Luciano
Relaix, Frederic
Redondo, Juan Miguel
Braun, Thomas
Serrano Sánchez, Antonio L.
Perdiguero, Eusebio, 1968-
Muñoz Cánoves, Pura, 1962-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chd4
NuRD
Lineage maintenance
Muscle stem cell
Regeneration
Satellite cells
Skeletal muscle
topic Chd4
NuRD
Lineage maintenance
Muscle stem cell
Regeneration
Satellite cells
Skeletal muscle
description Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We show that conditional deletion of the Chd4 gene in satellite cells results in failure to regenerate muscle after injury. This defect is principally associated with increased stem cell plasticity and lineage infidelity during the expansion of satellite cells, caused by de-repression of non-muscle-cell lineage genes in the absence of Chd4. Thus, CHD4 ensures that a transcriptional program that safeguards satellite cell identity during muscle regeneration is maintained. Given the therapeutic potential of muscle stem cells in diverse neuromuscular pathologies, CHD4 constitutes an attractive target for satellite cell-based therapies.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/48691
http://dx.doi.org/10.1016/j.stemcr.2021.07.022
url http://hdl.handle.net/10230/48691
http://dx.doi.org/10.1016/j.stemcr.2021.07.022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Stem Cell Reports. 2021;16(9):2089-98
info:eu-repo/grantAgreement/EC/H2020/741966
info:eu-repo/grantAgreement/EC/H2020/825825
info:eu-repo/grantAgreement/ES/1PE/SAF2016-77816-P
info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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