GEO series

iPSC data for the paper "Correction of dysregulated lipid metabolism normalizes gene expression in oligodendrocytes and prolongs lifespan in female poly-GA C9orf72 mouse model"

GSE285209 Homo sapiens (human) Single-nucleus RNA-seq 15 samples Submitted 2025/03/08 Platform GPL28038

At a glance

Single-nucleus RNA-seq · human · 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: Homo sapiens (human)
Samples: 15 samples: 4 × GA_CD vs 4 × GA_ctrl vs 4 × GFP_CD vs 3 × GFP_ctrlGroups 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 GSE285209 in finder → Find more human 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 GSE285209_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 PRJNA1201847 and SRA study SRP553283. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40216746) ↗

Study design

4 × GA_CD vs 4 × GA_ctrl vs 4 × GFP_CD vs 3 × GFP_ctrl

Supports a between-group comparison across 15 samples.

How we read this: 4 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

GSM8698381 GA_CD_1 GA_CD
GSM8698382 GA_CD_2 GA_CD
GSM8698383 GA_CD_3 GA_CD
GSM8698384 GA_CD_4 GA_CD
GSM8698385 GA_ctrl_1 GA_ctrl
GSM8698386 GA_ctrl_2 GA_ctrl
GSM8698387 GA_ctrl_3 GA_ctrl
GSM8698388 GA_ctrl_4 GA_ctrl
GSM8698389 GFP_CD_1 GFP_CD
GSM8698390 GFP_CD_2 GFP_CD
GSM8698391 GFP_CD_3 GFP_CD
GSM8698392 GFP_CD_4 GFP_CD
GSM8698393 GFP_ctrl_1 GFP_ctrl
GSM8698394 GFP_ctrl_2 GFP_ctrl
GSM8698395 GFP_ctrl_3 GFP_ctrl

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