Figure 7.

Model

Attenuated epigenetic suppression of muscle stem cell necroptosis is required for efficient regeneration of dystrophic muscles. CHD4/NuRD suppresses Ripk3 expression and thereby necroptosis in MuSCs of healthy muscles (bottom). Chronic dystrophy continuously evocates a demand for regeneration and persistent activation of MuSCs. Necroptosis secures removal of defective MuSCs that otherwise inhibit MuSC expansion in a non-cell-autonomous manner if not eliminated. Necroptosis in MuSCs is mediated by attenuated recruitment of CHD4/NuRD to the Ripk3 promoter in dystrophic muscles and leads to a lasting increase in necroptosis even in the absence of pro-necroptotic signals (“memory” effect) (top).