2026-08-05T15:45:29Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/103182025-05-20T08:40:50Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_19605col_20.500.12105_19616
Repisalud
author
Sreenivasan, Krishnamoorthy
author
Ianni, Alessandro
author
Künne, Carsten
author
Strilic, Boris
author
Günther, Stefan
author
Perdiguero, Eusebio
author
Krüger, Marcus
author
Spuler, Simone
author
Offermanns, Stefan
author
Gomez-del Arco, Pablo
author
Gómez-Del Arco, Pablo
author
Redondo, Juan Miguel
author
Munoz-Canoves, Pura
author
Kim, Johnny
author
Braun, Thomas
funder
German Centre for Cardiovascular Research
funder
German Center for Lung Research (Alemania)
funder
Fondation Leducq
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2020-06-10T07:41:13Z
2020-06-10T07:41:13Z
2020-05-19
Cell Rep. 2020; 31(7):107652
10.1016/j.celrep.2020.107652
2211-1247
Cell reports
32433961
http://hdl.handle.net/20.500.12105/10318
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.
eng
Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.
research article
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