GEO series

Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mouse model

GSE262778 Mus musculus (mouse) Single-nucleus RNA-seq 15 samples Submitted 2025/03/10 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 15 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: 15 samples: 15 samples, each with a distinct title — no replicated groupsGroups 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: Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 miceNature communications · 2025

Summary (written by the submitters)

These sequences support the following paper abstract: "Clinical and genetic research links altered cholesterol metabolism with ALS development and progression, yet pinpointing specific pathomechanisms remain challenging. We investigated how cholesterol dysmetabolism interacts with protein aggregation, demyelination, and neuronal loss in ALS.

Read the full summary ↓

Bulk RNAseq transcriptomics showed decreased cholesterol biosynthesis and increased cholesterol export in ALS mouse models (GA-Nes, GA-CFP, rNLS8) and patient samples (spinal cord), suggesting an adaptive response to cholesterol overload. Consequently, we assessed the efficacy of the cholesterol-binding drug 2-hydroxypropyl-β-cyclodextrin (CD) in a fast-progressing C9orf72 ALS mouse model with extensive poly-GA expression and myelination deficits. CD treatment normalized cholesteryl ester levels, lowered neurofilament light chain levels, and prolonged lifespan in female but not male GA-Nes mice, without impacting poly-GA aggregates. Single nucleus transcriptomics indicated that CD primarily affected oligodendrocytes, significantly restored myelin gene expression, increased density of myelinated axons, inhibited the disease-associated oligodendrocyte response, and downregulated the lipid-associated genes Plin4 and ApoD. These results suggest that reducing excess free cholesterol in the CNS could be a viable ALS treatment strategy.”

Published in

Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mice

Rezaei A, Kocsis-Jutka V, Gunes ZI et al. · Nature communications 2025 · PMID 40216746 · doi:10.1038/s41467-025-58634-4

This dataset

Open GSE262778 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 GSE262778_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 PRJNA1093372 and SRA study SRP498631. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40216746) ↗

Study design

15 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 15 sample titles: 15 distinct titles with little repetition. 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

GSM8178791 144-TG-Vehicle
GSM8178792 145-TG-Vehicle
GSM8178793 166-WT-Vehicle
GSM8178794 167-WT-Vehicle
GSM8178795 176-WT-Vehicle
GSM8178796 186-WT-Vehicle
GSM8178797 185-TG-Vehicle
GSM8178798 397-WT-CD
GSM8178799 399-TG-CD
GSM8178800 406-TG-CD
GSM8178801 408-TG-CD
GSM8178802 392-WT-CD
GSM8178803 412-TG-CD
GSM8178804 387-WT-CD
GSM8178805 379-WT-CD

Datasets on a similar topic

GSE291440 GA-Camk2a mouse RNAseq data for the manuscript by Rezaei et al: Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mouse model 21 samples shares c9orf72, oligodendrocytes, dysregulated, correction, normalizes, prolongs, lifespan, poly-ga
GSE289729 GA-CFP data for the manuscript "Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mouse model" 13 samples shares c9orf72, oligodendrocytes, dysregulated, correction, normalizes, prolongs, lifespan, poly-ga
GSE297313 TIA1-mediated stress granules promote the neurodegeneration of motor neurons through sequestrating mRNA of heat shock protein HSP70 family in C9orf72-poly-GA mice 7 samples shares c9orf72, poly-ga
GSE250633 A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD 27 samples shares c9orf72
GSE77681 C9orf72 is required for proper macrophage and microglial function in mice 21 samples shares c9orf72
GSE252888 Myeloid and lymphoid lineage C9orf72 regulates the IL-17 inflammatory axis in mice 12 samples shares c9orf72
GSE51685 Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (strand specific RNA-seq) 9 samples shares c9orf72
GSE333807 Single-nucleus multiomic profiling of hippocampus and frontal cortex in a C9orf72 knockout mouse model 52 samples shares c9orf72

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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.