Figure 1.

A Subpopulation of MuSCs Undergo Necroptotic or Apoptotic Cell Death in Chronic Muscle Disease

(A–C) Immunofluorescence staining of TA muscle cross-sections from control and mdx mice 2 weeks after CTX injury using antibodies against PAX7 and cleaved CASP3 to detect apoptosis (A) and PAX7 and RIPK3 to detect necroptosis (B) in MuSCs (n = 3 for each group). Scale bar, 25 μm.

(C) Quantification of cells identified in (A) and (B).

(D and E) EM images (MF, myofiber; # denotes chromatin condensation [apoptosis]; + denotes intact chromatin/nucleus [necrosis]; asterisk denotes MuSC disrupted membrane) (D) and quantification (E) of MuSCs from control (WT) and mdx mice undergoing apoptosis and necrosis (n = 3 for each group). Scale bar, 1 μm.

(F and G) Immunofluorescence staining for PAX7 and pMLKL to visualize (F) and quantify (G) MuSCs undergoing necroptosis in healthy (control) (n = 4) and Becker muscular dystrophy (BMD) patients (n = 4). Scale bar, 50 μm.

(H) Serum creatine kinase activity in control and BMD patients (n = 3 or 4 each).

Statistical analysis: ^∗p < 0.05 and ^∗∗p < 0.01, two-way ANOVA followed by Bonferroni post-test with alpha = 5%. All analyses indicated across the experiments were biological replicates unless otherwise stated.