GEO series

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

GSE291440 Mus musculus (mouse) Single-nucleus RNA-seq 21 samples Submitted 2025/03/11 Platform GPL18480

At a glance

Single-nucleus RNA-seq · mouse · 21 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: 21 samples: 21 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 GSE291440 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 GSE291440_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 PRJNA1233599 and SRA study SRP568901. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40216746) ↗

Study design

21 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 21 sample titles: 21 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

GSM8835717 GC11_cx_ctrl
GSM8835718 GC11_hp_ctrl
GSM8835719 GC16_cx_GACamk
GSM8835720 GC16_hp_GACamk
GSM8835721 GC20_cx_ctrl
GSM8835722 GC20_hp_ctrl
GSM8835723 GC23_cx_GACamk
GSM8835724 GC23_hp_GACamk
GSM8835725 GC30_cx_GACamk
GSM8835726 GC30_hp_GACamk
GSM8835727 GC31_cx_ctrl
GSM8835728 GC31_hp_ctrl
GSM8835729 GC34_cx_GACamk
GSM8835730 GC34_hp_GACamk
GSM8835731 GC35_cx_GACamk
GSM8835732 GC35_hp_GACamk
GSM8835733 GC37_cx_ctrl
GSM8835734 GC37_hp_ctrl
GSM8835735 GC38_cx_ctrl
GSM8835736 GC41_cx_GACamk
GSM8835737 GC41_hp_GACamk

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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
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