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Integrated stress response associated with dark microglia contributes to neurodegeneration [TRAP-seq]

GSE263679 Mus musculus (mouse) RNA-seq (gene expression) 29 samples Submitted 2024/12/23 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 29 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
29 samples: 7 conditions, mostly with about 4 replicates eachGroups 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
A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretionNeuron · 2025
Summary (written by the submitters)
Microglia, the brain’s primary resident immune cells, can assume various phenotypes with diverse functional outcomes on brain homeostasis. In Alzheimer’s disease (AD), where microglia are a leading causal cell type, the identity of microglia subsets that drive neurodegeneration remains unresolved. Here, we identify a microglia phenotype characterized by a conserved stress signaling pathway, the integrated stress response (ISR).
Read the full summary ↓
Using mouse models to activate or inhibit ISR in microglia, we show that ISR underlies the ultrastructurally distinct “dark” microglia subset linked to pathological synapse loss. Inducing microglial ISR in murine AD models exacerbates neurodegenerative pathologies, such as Tau pathology and synaptic terminal loss. Conversely, inhibiting microglial ISR in AD models ameliorates these pathologies. Mechanistically, we present evidence that ISR promotes the secretion of toxic long- chain lipids that impair neuron and oligodendrocyte homeostasis in vitro. Accordingly, inhibition of lipid synthesis in AD models ameliorates synaptic terminal loss. Our results demonstrate that activation of ISR within microglia represents a pathway contributing to neurodegeneration and suggest that this may be sustained, at least in part, by the secretion of long-chain lipids from ISR-activated microglia.
Published in
A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion
Flury A, Aljayousi L, Park HJ et al. · Neuron 2025 · PMID 39719704 · doi:10.1016/j.neuron.2024.11.018
This dataset
Open GSE263679 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 GSE263679_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 PRJNA1098742 and SRA study SRP500826. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39719704) ↗
Study design
7 conditions, mostly with about 4 replicates each
Control_TRAP ×5 iPKR_ASV ×5 5xFADTRAP ×4 Eif2ATRAP ×4 Control_iPKR_vehicle ×4 5xFADiPKR ×4 5xFADEif2ATRAP ×3

Supports a between-group comparison across 29 samples.

How we read this: 7 replicated groups read from 29 sample titles; they account for 29 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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