Diagenode

Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.


Sreenivasan K, Ianni A, Künne C, Strilic B, Günther S, Perdiguero E, Krüger M, Spuler S, Offermanns S, Gómez-Del Arco P, Redondo JM, Munoz-Canoves P, Kim J, Braun T

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.

Tags
Antibody

Share this article

Published
May, 2020

Source

Products used in this publication

  • Mouse IgG
    C15400001-15
    Mouse IgG
  • Mouse IgG
    C15410206
    Rabbit IgG

イベント

  • FASEB Biological Methylation: Fundamental Mechanisms
    Porto, Portugal
    Jul 28-Aug 1, 2024
 すべてのイベントを見る

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy