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Age-associated dysregulation of post-synaptic mitochondria perturbs re-innervation kinetics

GSE296807 Mus musculus (mouse) Single-nucleus RNA-seq 26 samples Submitted 2025/05/16 Platform GPL34328
At a glance

Single-nucleus RNA-seq · mouse · 26 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). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
26 samples: 4 × PBS_d0 vs 4 × AAV_d0 vs 3 × AAV_d14 vs 3 × PBS_d14Groups 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.
Summary (written by the submitters)
Age-associated degeneration of neuromuscular junctions (NMJs) contributes to sarcopenia and motor decline, yet the mechanisms linking mitochondrial dysfunction to impaired NMJ regeneration in aging remain poorly defined. Here, we demonstrate that post-synaptic mitochondria are significantly diminished in both quantity and bioenergetic function in aged skeletal muscle, correlating with increased denervation and delayed reinnervation following nerve injury.
Read the full summary ↓
Single-nucleus RNA sequencing of myofibers before and after sciatic nerve crush revealed that sub-synaptic myonuclei in aged muscle exhibit attenuated induction of mitochondrial gene programs, including oxidative phosphorylation, biogenesis, and import. To test whether these deficits are causal, we developed a muscle-specific CRISPR genome editing approach targeting CHCHD2 and CHCHD10—two nuclear-encoded mitochondrial proteins that localize to the intermembrane space and interact with the mitochondrial contact site and cristae organizing system (MICOS). Knockout of CHCHD2/CHCHD10 in young muscle recapitulated aged phenotypes, including mitochondrial disorganization, reduced ATP production, NMJ fragmentation, and delayed reinnervation. Transcriptional profiling of NMJ nuclei from knockout muscles revealed impaired pseudotime progression, failure to activate mitochondrial remodeling programs, and elevated stress signatures. These findings establish a critical role for sub-synaptic mitochondrial integrity in sustaining NMJ stability and regenerative capacity and identify CHCH domain-containing proteins as key regulators of post-synaptic mitochondrial function during aging and injury.
This dataset
Open GSE296807 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 GSE296807_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 PRJNA1261070 and SRA study SRP584280. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
4 × PBS_d0 vs 4 × AAV_d0 vs 3 × AAV_d14 vs 3 × PBS_d14

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 26 sample titles; they account for 14 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
Datasets on a similar topic

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