GEO series

Tissue nanotransfection-mediated induction of neurogenic programs promotes myoprotective responses in denervated skeletal muscle

GSE334940 Mus musculus Expression profiling by high throughput sequencing 15 samples Submitted 2026/08/07 Platform GPL34290

Summary

Peripheral nerve injuries often result in prolonged skeletal muscle denervation, leading to progressive atrophy, fibrosis, neuromuscular instability, and loss of regenerative capacity before axons can reinnervate distal targets. Here, we developed a non-viral strategy using tissue nanotransfection (TNT) to deliver the neurogenic transcription factor cocktail Ascl1, Brn2, and Myt1l (ABM) directly to denervated skeletal muscle. In vitro, ABM-transfected myoblasts sustained expression of the reprogramming factors, acquired neuron-like morphologies, and upregulated neuronal markers including Tuj1, Map2, and Syp. RNA sequencing confirmed broad activation of neurogenic transcriptional programs, with enrichment of pathways associated with neuronal fate commitment, neuron differentiation, axon guidance, synaptogenesis, and developmental signaling. In a mouse model of sciatic nerve resection, TNT enabled localized ABM expression in denervated gastrocnemius muscle. ABM-TNT treatment accelerated resolution of denervation-associated fibrillation potentials and showed trends toward improved twitch and tetanic torque, compound muscle action potential amplitudes, and muscle mass preservation. Transcriptomic profiling of treated muscles 5 weeks after injury revealed distinct gene expression programs enriched for muscle regeneration, neuromuscular organization, trophic support, extracellular matrix remodeling, angiogenesis, myogenesis, and metabolic adaptation. Network analyses further identified activation of neurogenic regulators, neurotrophic signaling, and vascular-support pathways. These findings establish TNT-mediated ABM delivery as a non-viral platform for inducing neurogenic and myoprotective programs in denervated muscle and suggest a strategy to preserve muscle viability during the prolonged interval required for peripheral nerve regeneration.

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Direct links to NCBI, no account and no request form: the whole study as GSE334940_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 15 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1476954 and SRA study SRP708378. Searching any of these in the dataset finder brings you back here.

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Study design

5 × Control vs 5 × Sham vs 5 × ABM

Supports a between-group comparison across 15 samples.

3 replicated groups read from 15 sample titles; they account for 15 of them. Check it against the sample list below before relying on it.

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