Rotator cuff tear (RCT) stands as a primary cause of shoulder pain and disability, frequently triggering muscle degeneration characterized by muscle atrophy, fatty infiltration, and fibrosis. Skeletal muscle displays remarkable plasticity under both physiological and pathological conditions. Single-nucleus RNA sequencing (snRNA-seq) was applied to reveal transcriptional changes of the supraspinatus muscle after RCT. The supraspinatus muscles from habitual shoulder dislocation patients (n=3) and RCT patients (n=3) were obtained. Diverse bioinformatics analyses, encompassing unsupervised clustering, functional enrichment analysis, trajectory analysis, regulatory network inference, and cell–cell communication prediction, were employed to elucidate the transcriptomic changes within individual cell types. A total of 16893 muscle nuclei (normal vs. RCT: 8990 vs 7903) were classified into 10 nuclear types according to the known cell markers. In response to RCT, trajectory analysis revealed that ANKRD1 + type II myonuclei deviated away from the normal type IIx and type IIa myonuclei. Signature genes in ANKRD1 + type II myonuclei included RUNX1, GADD45A, STAT3. Trajectory results also showed progression from ATP2A2 + type I myonuclei in the normal group to ANKRD1 + type I myonuclei in the RCT group. The gene regulatory network analysis of myonuclei captured a group of atrophy and fatty infiltration-related regulons (KLF5, KLF10, FOSL1 and BHLHE40) whose activities were enhanced in the ANKRD1 + myonuclei. We also investigated the transcriptomic alterations in the fibro/adipogenic progenitors (FAPs), muscle satellite cells (MuSCs), and characterized their signature responses to RCT. By predicting the cell–cell interactions, we observed the communication alterations between myofibers and muscle resident cells following RCT. Our findings revealed the plasticity of muscle cells in response to RCT and offered a valuable insight for exploring the molecular mechanisms and potential therapeutic targets for RCT.
Sun et al. (Mon,) studied this question.