Cellular Remodeling of Skeletal Muscle Following Botulinum Toxin A Injection: A Single-Nucleus RNA Sequencing Study.

BACKGROUND

Botulinum toxin type A (BoNT) is widely used in aesthetic and reconstructive surgery, yet its effects on skeletal muscle tissue at the cellular level remain incompletely defined.

METHODS

Public single-nucleus RNA sequencing data from murine skeletal muscle (GEO: GSE267910) were reanalyzed, including control, BoNT-treated, denervation, and MuSK knockout models. Cell populations, cellular composition, and cell-type-specific transcriptional changes were systematically evaluated.

RESULTS

Seven major skeletal muscle cell populations were identified. Cell-type identity was preserved across experimental conditions, with no emergence of novel lineages following BoNT injection. BoNT treatment significantly altered cellular composition, characterized by increased fibro-adipogenic progenitors and reduced myonuclei. Transcriptional responses were highly cell-type specific, with prominent changes in fibro-adipogenic progenitors and myonuclei. Compared with denervation, BoNT-induced changes showed relatively limited immune activation.

CONCLUSIONS

BoNT remodels skeletal muscle primarily by altering the proportion and functional state of existing cell types rather than changing cellular lineage identity, suggesting preservation of cellular lineage identity at the transcriptomic level.

LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .