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dc.contributor.authorSreenivasan, Krishnamoorthy
dc.contributor.authorIanni, Alessandro
dc.contributor.authorKünne, Carsten
dc.contributor.authorStrilic, Boris
dc.contributor.authorGünther, Stefan
dc.contributor.authorPerdiguero, Eusebio
dc.contributor.authorKrüger, Marcus
dc.contributor.authorSpuler, Simone
dc.contributor.authorOffermanns, Stefan
dc.contributor.authorGomez-del Arco, Pablo 
dc.contributor.authorGómez-Del Arco, Pablo 
dc.contributor.authorRedondo, Juan Miguel 
dc.contributor.authorMunoz-Canoves, Pura 
dc.contributor.authorKim, Johnny
dc.contributor.authorBraun, Thomas
dc.date.accessioned2020-06-10T07:41:13Z
dc.date.available2020-06-10T07:41:13Z
dc.date.issued2020-05-19
dc.identifier.citationCell Rep. 2020; 31(7):107652es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/10318
dc.description.abstractSomatic stem cells expand massively during tissue regeneration, which might require control of cell fitness, allowing elimination of non-competitive, potentially harmful cells. How or if such cells are removed to restore organ function is not fully understood. Here, we show that a substantial fraction of muscle stem cells (MuSCs) undergo necroptosis because of epigenetic rewiring during chronic skeletal muscle regeneration, which is required for efficient regeneration of dystrophic muscles. Inhibition of necroptosis strongly enhances suppression of MuSC expansion in a non-cell-autonomous manner. Prevention of necroptosis in MuSCs of healthy muscles is mediated by the chromatin remodeler CHD4, which directly represses the necroptotic effector Ripk3, while CHD4-dependent Ripk3 repression is dramatically attenuated in dystrophic muscles. Loss of Ripk3 repression by inactivation of Chd4 causes massive necroptosis of MuSCs, abolishing regeneration. Our study demonstrates how programmed cell death in MuSCs is tightly controlled to achieve optimal tissue regeneration.es_ES
dc.description.sponsorshipThis work was supported by the DFG (Cardiopulmonary Institute [CPI], SFB TRR81 TP A02 and SFB 1213, TP A02 and B02); the LOEWE Center for Cell and Gene Therapy; the German Center for Cardiovascular Research; the European Research Area Network on Cardiovascular Diseases (grant CLARIFY); and Foundation Leducq. P.G.A. is supported by MICINN (SAF2016-77816-P). P.M.-C. acknowledges funding from grants RTI2018-096068-B-I00, MDM-2014-0370, SEV-2015-0505, ERC-2016-AdG-741966, La Caixa-HEALTH-HR17-00040, MDA, UPGRADE-H2020-825825, AFM, and DPP-E. T.B. is a member of the German Center for Cardiovascular Research (DZHK) and of the German Center for Lung Research (DZL)es_ES
dc.language.isoenges_ES
dc.publisherCell Press es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleAttenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID32433961es_ES
dc.format.volume31es_ES
dc.format.number7es_ES
dc.format.page107652es_ES
dc.identifier.doi10.1016/j.celrep.2020.107652es_ES
dc.contributor.funderGerman Centre for Cardiovascular Research 
dc.contributor.funderGerman Center for Lung Research (Alemania) 
dc.contributor.funderFondation Leducq 
dc.contributor.funderMinisterio de Ciencia e Innovación (España) 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn2211-1247es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.celrep.2020.107652es_ES
dc.identifier.journalCell reportses_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Raras
dc.repisalud.orgCNICCNIC::Grupos de investigación::Laboratorio de Regeneración Tisulares_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamaciónes_ES
dc.repisalud.institucionCNICes_ES
dc.repisalud.institucionISCIII
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/741966es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2016-77816-Pes_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional