# Single‐nucleus transcriptomics reveals subsets of degenerative myonuclei after rotator cuff tear‐induced muscle atrophy

## TL;DR

This study uses single-nucleus RNA sequencing to uncover how muscle cells change after a rotator cuff tear, revealing new insights into muscle atrophy and potential treatments.

## Contribution

The study identifies novel transcriptional changes and cell communication patterns in muscle cells following a rotator cuff tear.

## Key findings

- Trajectory analysis revealed progression from normal myonuclei to ANKRD1+ myonuclei linked to atrophy and fatty infiltration.
- Transcriptomic changes in fibro/adipogenic progenitors and muscle satellite cells were observed after RCT.
- Altered communication between myofibers and muscle-resident cells was identified following RCT.

## Abstract

Rotator cuff tear (RCT) is the primary cause of shoulder pain and disability and frequently trigger muscle degeneration characterised by muscle atrophy, fatty infiltration and fibrosis. Single‐nucleus RNA sequencing (snRNA‐seq) was used to reveal the transcriptional changes in the supraspinatus muscle after RCT. Supraspinatus muscles were obtained from patients with habitual shoulder dislocation (n = 3) and RCT (n = 3). In response to the RCT, trajectory analysis showed progression from normal myonuclei to ANKRD1+ myonuclei, which captured atrophy‐and fatty infiltration‐related regulons (KLF5, KLF10, FOSL1 and BHLHE40). Transcriptomic alterations in fibro/adipogenic progenitors (FAPs) and muscle satellite cells (MuSCs) have also been studied. By predicting cell–cell interactions, we observed communication alterations between myofibers and muscle‐resident cells following RCT. Our findings reveal the plasticity of muscle cells in response to RCT and offer valuable insights into the molecular mechanisms and potential therapeutic targets of RCT.

We performed single‐nucleus RNA‐seq to reveal the transcriptional heterogeneity in myofibers after rotator cuff tear (RCT). Gene signatures of all muscle tissue populations were identified after RCT to reveal the potential transitions of myofibers and other resident cells. Our findings offered a valuable insight for exploring the molecular mechanisms and potential therapeutic targets for RCT.