Sreenivasan, 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, 1962-2021-10-192021-10-192021Sreenivasan 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.2021.07.0222213-6711http://hdl.handle.net/10230/48691Regeneration 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.application/pdfeng© 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/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.stemcr.2021.07.022Chd4NuRDLineage maintenanceMuscle stem cellRegenerationSatellite cellsSkeletal muscleinfo:eu-repo/semantics/openAccess