Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance.

ABSTRACT: The neuromuscular junction (NMJ) is the synapse formed between motor neurons and skeletal muscle fibers. Its stability relies on the continued expression of genes in a subset of myonuclei, called NMJ myonuclei. Here, we use single-nuclei RNA-sequencing (snRNA-seq) to identify numerous NMJ-specific transcripts. To elucidate how the NMJ transcriptome is regulated, we also performed snRNA-seq on sciatic nerve transected, botulinum toxin injected, and Musk knockout muscles. The data show that NMJ gene expression is not only driven by agrin-Lrp4/MuSK signaling but is also affected by electrical activity and trophic factors other than agrin. By selecting the three NMJ genes Etv4, Lrtm1, and Pdzrn4, we further characterize novel contributors to NMJ stability and function. AAV-mediated overexpress

SUBMITTER: Ham AS 

PROVIDER: S-EPMC11882927 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature