CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration

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-

CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration

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dc.contributor.author Sreenivasan, Krishnamoorthy
dc.contributor.author Rodríguez de la Rosa, Alejandra
dc.contributor.author Kim, Johnny
dc.contributor.author Mesquita, Diana
dc.contributor.author Segalés Dalmau, Jessica
dc.contributor.author Gómez del Arco, Pablo
dc.contributor.author Espejo, Isabel
dc.contributor.author Ianni, Alessandro
dc.contributor.author Di Croce, Luciano
dc.contributor.author Relaix, Frederic
dc.contributor.author Redondo, Juan Miguel
dc.contributor.author Braun, Thomas
dc.contributor.author Serrano Sánchez, Antonio L.
dc.contributor.author Perdiguero, Eusebio, 1968-
dc.contributor.author Muñoz Cánoves, Pura, 1962-
dc.date.accessioned 2021-10-19T06:09:48Z
dc.date.available 2021-10-19T06:09:48Z
dc.date.issued 2021
dc.description.abstract 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.
dc.description.sponsorship 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 ).
dc.format.mimetype application/pdf
dc.identifier.citation Sreenivasan K, Rodríguez-delaRosa A, Kim J, Mesquita D, Segalés J, Arco PG, Espejo I, Ianni A, Di Croce L, Relaix F, Redondo JM, Braun T, Serrano AL, Perdiguero E, Muñoz-Cánoves P. CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. Stem Cell Reports. 2021;16(9):2089-98. DOI: 10.1016/j.stemcr.2021.07.022
dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2021.07.022
dc.identifier.issn 2213-6711
dc.identifier.uri http://hdl.handle.net/10230/48691
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Stem Cell Reports. 2021;16(9):2089-98
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-77816-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096068
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Chd4
dc.subject.keyword NuRD
dc.subject.keyword Lineage maintenance
dc.subject.keyword Muscle stem cell
dc.subject.keyword Regeneration
dc.subject.keyword Satellite cells
dc.subject.keyword Skeletal muscle
dc.title CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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