GEO series

Dose-dependent CHCHD10 dysregulation affects motor neuron disease severity and creatine metabolism

GSE276449 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2025/05/30 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 15 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 15 samples: 5 × Het vs 5 × Hom vs 5 × WTGroups 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: Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolismActa neuropathologica communications · 2025

Summary (written by the submitters)

Dominant defects in CHCHD10, a mitochondrial intermembrane space protein, lead to a range of neurological and muscle phenotypes including amyotrophic lateral sclerosis. Many patients present with spinal muscular atrophy Jokela type (SMAJ), which is caused by a heterozygous p.G66V variant. While most disease variants lead to aggregation of CHCHD10 and activation of proteotoxic stress responses, the pathogenic mechanisms of the p.G66V variant have been less investigated.

Read the full summary ↓

We report here the first homozygous CHCHD10 patient, with variant p.G66V. We compare the metabolic findings in heterozygous and homozygous SMAJ patient skin fibroblasts, and in motor neurons differentiated from patient-specific stem cells as well as a novel mouse model of SMAJ. Our findings show that p.G66V variant leads to dose-depended reduction of the CHCHD10 protein in a cell type specific manner. In addition, CHCHD10 p.G66V dysregulates energy metabolism, leading to altered redox balance and energy buffering by creatine metabolism.

Published in

Dose-dependent CHCHD10 dysregulation dictates motor neuron disease severity and alters creatine metabolism

Harjuhaahto S, Jokela M, Rajendran J et al. · Acta neuropathologica communications 2025 · PMID 40400037 · doi:10.1186/s40478-025-02039-3

This dataset

Open GSE276449 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 GSE276449_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1157393 and SRA study SRP530747. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40400037) ↗

Study design

5 × Het vs 5 × Hom vs 5 × WT

Supports a between-group comparison across 15 samples.

How we read this: 3 replicated groups read from 15 sample titles; they account for 15 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

GSM8498697 Het_1 Het
GSM8498698 Het_2 Het
GSM8498699 Het_3 Het
GSM8498700 Het_4 Het
GSM8498701 Het_5 Het
GSM8498702 Hom_1 Hom
GSM8498703 Hom_2 Hom
GSM8498704 Hom_3 Hom
GSM8498705 Hom_4 Hom
GSM8498706 Hom_5 Hom
GSM8498707 WT_1 WT
GSM8498708 WT_2 WT
GSM8498709 WT_3 WT
GSM8498710 WT_4 WT
GSM8498711 WT_5 WT

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Search all mouse RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.