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

Area of Science:

• Skeletal Muscle Biology
• Cellular and Molecular Medicine
• Regenerative Medicine

Background:

• Botulinum toxin type A (BoNT) is extensively utilized in aesthetic and reconstructive surgery.
• Its precise cellular-level effects on skeletal muscle tissue are not fully understood.

Purpose of the Study:

• To investigate the cellular and transcriptomic impact of BoNT on skeletal muscle.
• To compare BoNT-induced changes with denervation and genetic muscle disruption models.

Main Methods:

• Reanalysis of public single-nucleus RNA sequencing data from murine skeletal muscle (GEO: GSE267910).
• Evaluation of cell populations, composition, and cell-type-specific transcriptional changes under control, BoNT, denervation, and MuSK knockout conditions.

Main Results:

• Seven major skeletal muscle cell populations were identified, with cell-type identity maintained across conditions.
• BoNT treatment significantly altered cellular composition, increasing fibro-adipogenic progenitors and reducing myonuclei.
• Transcriptional changes were cell-type specific, with notable alterations in fibro-adipogenic progenitors and myonuclei; immune activation was limited compared to denervation.

Conclusions:

• BoNT remodels skeletal muscle by modifying the proportion and function of existing cell types.
• Cellular lineage identity is preserved at the transcriptomic level following BoNT treatment.