Sreenivasan, Krishnamoorthy, Ianni, Alessandro ORCID: 0000-0001-7398-589X, Kuenne, Carsten, Strilic, Boris, Guenther, Stefan, Perdiguero, Eusebio, Krueger, Marcus, Spuler, Simone, Offermanns, Stefan, Gomez-del Arco, Pablo ORCID: 0000-0001-6748-7157, Miguel Redondo, Juan, Munoz-Canoves, Pura, Kim, Johnny and Braun, Thomas (2020). Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles. Cell Reports, 31 (7). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sreenivasan, KrishnamoorthyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ianni, AlessandroUNSPECIFIEDorcid.org/0000-0001-7398-589XUNSPECIFIED
Kuenne, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strilic, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenther, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perdiguero, EusebioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spuler, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offermanns, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomez-del Arco, PabloUNSPECIFIEDorcid.org/0000-0001-6748-7157UNSPECIFIED
Miguel Redondo, JuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munoz-Canoves, PuraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, JohnnyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braun, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-333445
DOI: 10.1016/j.celrep.2020.107652
Journal or Publication Title: Cell Reports
Volume: 31
Number: 7
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SKELETAL-MUSCLE; SATELLITE CELLS; MUSCULAR-DYSTROPHY; CHROMATIN; APOPTOSIS; DEATH; INFLAMMATION; MAINTENANCE; MECHANISMS; INJURYMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33344

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