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Inflammatory microglia with lysosomal and lipid dysfunction drive chronic progressive demyelination

GSE296313 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2026/07/16 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 8 conditions, mostly in duplicateGroups 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)
Dysfunctional immune responses impair tissue repair and contribute to neurodegeneration. We examined whether chronic demyelination could drive inflammation towards a pathological, tissue-destructive state. Comparative analysis of genetic and toxic models of acute and chronic demyelination identified a disease-promoting microglial state, characterized by sustained pro-inflammatory activation and enhanced myelin-destructive activity in chronic demyelination.
Read the full summary ↓
Mechanistically, they exhibited lysosomal cholesterol sequestration with reduced lipid droplet formation. Lipidomic profiling showed defective cholesterol esterification, while transcriptomics uncovered a dysregulated metabolic program marked by upregulated cholesterol synthesis and diminished sterol efflux. Restoring cholesterol homeostasis with a brain-penetrant desmosterol mimetic normalized microglial function, reduced pro-inflammatory activation (e.g. C-C Motif Chemokine Ligand 4 expression), mitigated myelin damage, and improved motor performance in a mouse model of leukodystrophy. Our findings uncover a previously unrecognized pro-inflammatory microglial state characterized by lysosomal dysfunction and increased myelin reactivity, highlighting a novel therapeutic target for demyelinating disorders.
This dataset
Open GSE296313 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 GSE296313_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 PRJNA1258892 and SRA study SRP583084. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, mostly in duplicate
brain cells, FACS sorted, 4month old, ctrl, ×3 brain cells, FACS sorted, 8month old, ctrl, ×3 brain cells, FACS sorted, 8month old, Plp1Tg, ×3 brain cells, ctrl, ×2 brain cells, Plp1Tg, ×2 brain cells, acute cuprizone treatment (6 wee… ×2 brain cells, chronic cuprizone treatment (12 … ×2 brain cells, FACS sorted, 4month old, Plp1Tg, ×2 +1 more

Supports a between-group comparison across 19 samples.

How we read this: 8 replicated groups read from 20 sample titles; they account for 19 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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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.