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Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance (snRNA-Seq)

GSE267910 Mus musculus (mouse) Single-nucleus RNA-seq 12 samples Submitted 2025/02/10 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 12 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue).
Organism: Mus musculus (mouse)
Samples: 12 samples: 2 × In_GAS vs 2 × In_TA vs 2 × Den_GAS vs 2 × Den_TAGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenanceNature communications · 2025

Summary (written by the submitters)

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 undescribed 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.

Read the full summary ↓

These 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 three previously undescribed NMJ genes Etv4, Lrtm1 and Pdzrn4, we further characterize novel contributors to NMJ stability and function. AAV-mediated overexpression and AAV-CRISPR/Cas9-mediated knockout show that Etv4 is sufficient to upregulate expression of ~50% of the NMJ genes in non-synaptic myonuclei, while muscle-specific knockout of Pdzrn4 induces NMJ fragmentation. Further investigation of Pdzrn4 revealed that it localizes to the Golgi apparatus and interacts with MuSK protein. Collectively, our data provide a rich resource of NMJ transcripts, highlight the importance of ETS transcription factors at the NMJ and suggest a novel pathway for NMJ post-translational modifications.

Published in

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

Ham AS, Lin S, Tse A et al. · Nature communications 2025 · PMID 40044687 · doi:10.1038/s41467-025-57487-1

This dataset

Open GSE267910 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE267910_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1113625 and SRA study SRP512446. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40044687) ↗

Study design

2 × In_GAS vs 2 × In_TA vs 2 × Den_GAS vs 2 × Den_TA

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 8 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8281470 In_GAS_1 In_GAS
GSM8281471 In_GAS_2 In_GAS
GSM8281472 In_TA_1 In_TA
GSM8281473 In_TA_2 In_TA
GSM8281474 Den_GAS_1 Den_GAS
GSM8281475 Den_GAS_2 Den_GAS
GSM8281476 Den_TA_1 Den_TA
GSM8281477 Den_TA_2 Den_TA
GSM8281478 BoTX
GSM8281479 BoTX_Ctrl
GSM8281480 MuskKO_Ctrl
GSM8281481 MuskKO

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GSE303861 The growth factor FGF21 maintains neuromuscular junction through histone deacetylase HDAC4 in denervation-induced skeletal muscle atrophy 4 samples shares neuromuscular, skeletal
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