Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles

Somatic 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 fracti...

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Autores: Sreenivasan, Krishnamoorthy, Ianni, Alessandro, Künne, Carsten, Strilic, Boris, Günther, Stefan, Perdiguero, Eusebio, 1968-, Krüger, Marcus, Spuler, Simone, Offermanns, Stefan, Gómez del Arco, Pablo, Redondo, Juan Miguel, Muñoz Cánoves, Pura, 1962-, Kim, Johnny, Braun, Thomas
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44880
Acesso em linha:http://hdl.handle.net/10230/44880
http://dx.doi.org/10.1016/j.celrep.2020.107652
Access Level:acceso abierto
Palavra-chave:Chd4/NuRD
Ripk3
Muscle dystrophy
Muscle stem cells
Necroptosis
Regeneration
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spelling Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic musclesSreenivasan, KrishnamoorthyIanni, AlessandroKünne, CarstenStrilic, BorisGünther, StefanPerdiguero, Eusebio, 1968-Krüger, MarcusSpuler, SimoneOffermanns, StefanGómez del Arco, PabloRedondo, Juan MiguelMuñoz Cánoves, Pura, 1962-Kim, JohnnyBraun, ThomasChd4/NuRDRipk3Muscle dystrophyMuscle stem cellsNecroptosisRegenerationSomatic 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.This 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).Elsevier202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44880http://dx.doi.org/10.1016/j.celrep.2020.107652reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCell Rep. 2020; 31(7):107652info:eu-repo/grantAgreement/EC/H2020/741966info:eu-repo/grantAgreement/ES/1PE/SAF2016-77816-Pinfo:eu-repo/grantAgreement/EC/H2020/825825© 2020 The Author(s). 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:10230/448802026-05-29T05:05:01Z
dc.title.none.fl_str_mv Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
title Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
spellingShingle Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
Sreenivasan, Krishnamoorthy
Chd4/NuRD
Ripk3
Muscle dystrophy
Muscle stem cells
Necroptosis
Regeneration
title_short Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
title_full Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
title_fullStr Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
title_full_unstemmed Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
title_sort Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles
dc.creator.none.fl_str_mv Sreenivasan, Krishnamoorthy
Ianni, Alessandro
Künne, Carsten
Strilic, Boris
Günther, Stefan
Perdiguero, Eusebio, 1968-
Krüger, Marcus
Spuler, Simone
Offermanns, Stefan
Gómez del Arco, Pablo
Redondo, Juan Miguel
Muñoz Cánoves, Pura, 1962-
Kim, Johnny
Braun, Thomas
author Sreenivasan, Krishnamoorthy
author_facet Sreenivasan, Krishnamoorthy
Ianni, Alessandro
Künne, Carsten
Strilic, Boris
Günther, Stefan
Perdiguero, Eusebio, 1968-
Krüger, Marcus
Spuler, Simone
Offermanns, Stefan
Gómez del Arco, Pablo
Redondo, Juan Miguel
Muñoz Cánoves, Pura, 1962-
Kim, Johnny
Braun, Thomas
author_role author
author2 Ianni, Alessandro
Künne, Carsten
Strilic, Boris
Günther, Stefan
Perdiguero, Eusebio, 1968-
Krüger, Marcus
Spuler, Simone
Offermanns, Stefan
Gómez del Arco, Pablo
Redondo, Juan Miguel
Muñoz Cánoves, Pura, 1962-
Kim, Johnny
Braun, Thomas
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chd4/NuRD
Ripk3
Muscle dystrophy
Muscle stem cells
Necroptosis
Regeneration
topic Chd4/NuRD
Ripk3
Muscle dystrophy
Muscle stem cells
Necroptosis
Regeneration
description Somatic 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
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/10230/44880
http://dx.doi.org/10.1016/j.celrep.2020.107652
url http://hdl.handle.net/10230/44880
http://dx.doi.org/10.1016/j.celrep.2020.107652
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Rep. 2020; 31(7):107652
info:eu-repo/grantAgreement/EC/H2020/741966
info:eu-repo/grantAgreement/ES/1PE/SAF2016-77816-P
info:eu-repo/grantAgreement/EC/H2020/825825
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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