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Deletion of the X chromosome gene Kdm6a in microglia is protective in the multiple sclerosis model, female and male

GSE246008 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/10/15 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 24 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
Deletion of the X-chromosomal gene Kdm6a in microglia of female mice ameliorates neuroinflammation and restores translatome profilesScience translational medicine · 2025
Summary (written by the submitters)
Multiple sclerosis (MS) exhibits a sex difference in susceptibility with females affected more frequently than males. Sexual dimorphisms may be due to differences in sex hormones, sex chromosomes, or both. Regarding sex chromosomes, some X chromosome genes escape X-inactivation and have higher expression in females (XX) compared to males (XY).
Read the full summary ↓
The Genotype Tissue Expression Project (GTEx) has found that 37% of all genes exhibit sex biased expression which is tissue-specific and cell-specific, but the etiology and ramifications of this sex difference remain unknown. Kdm6a is an X chromosome gene that escapes X-inactivation and encodes for a histone demethylase which can modulate autosomal gene expression. Given the important role of microglia in neurodegenerative diseases, we created a tissue-specific and cell-specific conditional knock out (cKO) of Kdm6a in microglia and induced experimental autoimmune encephalomyelitis (EAE), the most widely used mouse model for MS. Deletion of Kdm6a in microglia ameliorated EAE. Gene expression analysis of spinal cord microglia during EAE in the Kdm6a cKO revealed downregulation of degeneration associated microglial markers and upregulation of resting microglial markers compared to EAE in wild type. Genome wide transcriptome analyses demonstrated reversal of the EAE associated transcriptome in microglia in Kdm6a cKO mice, instead aligning with that of the transcriptome of microglia in healthy mice. Finally, there was a sex difference in the effect of selective deletion of Kdm6a in microglia whereby EAE was abrogated in females more significantly than in males. Together, this demonstrates that the X-escapee Kdm6a is disease promoting in microglia of females with neurodegenerative disease.
Published in
Deletion of the X-chromosomal gene Kdm6a in microglia of female mice ameliorates neuroinflammation and restores translatome profiles
Itoh Y, Itoh N, Wendin S et al. · Science translational medicine 2025 · PMID 41091915 · doi:10.1126/scitranslmed.adq3401
This dataset
Open GSE246008 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 GSE246008_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 PRJNA1031097 and SRA study SRP467935. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41091915) ↗
Study design
24 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 24 sample titles: 24 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
Datasets on a similar topic

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