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Astrocytic Sox9 preserves cognitive function in models of Alsheimer's Disease [RNA-Seq]

GSE294900 Mus musculus (mouse) RNA-seq (gene expression) 22 samples Submitted 2026/01/06 Platform GPL21626
At a glance

RNA-seq (gene expression) · mouse · 22 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
22 samples: 7 conditions, mostly in triplicateGroups 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
Astrocytic Sox9 overexpression in Alzheimer's disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive functionNature neuroscience · 2026
Summary (written by the submitters)
Astrocytes play essential roles in the brain and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, our knowledge of how astrocytes contribute to disease pathogenesis is incomplete, accordingly harnessing their biology towards therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer’s Disease (AD) models.
Read the full summary ↓
We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes through the regulation of the phagocytic receptor MEGF10, which is sufficient to preserve cognitive function in AD models. Collectively, these studies highlight new roles for astrocytic Sox9 during aging and AD, while identifying Sox9-MEGF10 signaling as a prospective astrocyte-based therapeutic approach to ameliorate cognitive decline in neurodegenerative disease.
Published in
Astrocytic Sox9 overexpression in Alzheimer's disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function
Choi DJ, Murali S, Kwon W et al. · Nature neuroscience 2026 · PMID 41272323 · doi:10.1038/s41593-025-02115-w
This dataset
Open GSE294900 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 GSE294900_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 PRJNA1252011 and SRA study SRP579407. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41272323) ↗
Study design
7 conditions, mostly in triplicate
AD_Sox9-Overexpression_Hippocampal_Astrocytes ×4 WT_young_4month_Hippocampal_Astrocyte ×3 WT_aged_18month_Hippocampal_Astrocyte ×3 WT_young_4month_Hippocampal_Sox9flox_Astrocyt… ×3 Sox9-KO_young_4month_Hippocampal_Sox9flox_Ast… ×3 Sox9-KO_aged_18month_Hippocampal_Sox9flox_Ast… ×3 AD_control_Hippocampal_Astrocytes ×3

Supports a case/control comparison: 4 samples read as cases, 12 as controls.

How we read this: 7 replicated groups read from 22 sample titles; they account for 22 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
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