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REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function

GSE293026 Mus musculus (mouse) RNA-seq (gene expression) 26 samples Submitted 2026/01/14 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 26 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
26 samples: 6 conditions, mostly with about 5 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
REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic functionProceedings of the National Academy of Sciences of the United States of America · 2026
Summary (written by the submitters)
The molecular circadian clock is a ubiquitous transcriptional-translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The druggable nuclear receptors REV-ERB-ɑ (gene: Nr1d1) and REV-ERB-.Beta. (gene: Nr1d2) are components of the core circadian clock. REV-ERB proteins regulate neuroinflammatory responses, synaptic pruning, and protein aggregation, though the cell type-specific effects and relative compensatory effects of REV-ERB-ɑ AND -.Beta.
Read the full summary ↓
in the brain are unknown. To study the CNS functions of REV-ERBs, we developed mouse lines with global or astrocyte-specific, conditional knockout of both REV-ERB-ɑ and -.Beta.. We demonstrate that inducible post-natal global deletion of REV-ERB-ɑ and -.Beta. in vivo results in robust spontaneous astrocyte activation and increases gene expression of disease-relevant pathways such as protein catabolism, complement, and oxidative stress. Furthermore, in vivo astrocyte-specific deletion of REV-ERB-ɑ/-.Beta. recapitulates the spontaneous astrocyte activation phenotype seen in global REV-ERB-ɑ/-.Beta. KO mice, as well as in mice with deletion of key core clock gene Bmal1, indicating that REV-ERBs regulate astrocyte activation in a cell-autonomous manner downstream of the core circadian clock. REV-ERB-ɑ/-.Beta. repress transcription of Stat3 in the brain, and deletion of REV-ERBs in astrocytes induces increased astrocytic STAT3 expression and downstream STAT3-mediated gene changes, a mechanistic link to the astrocyte reactivity shift. This astrocyte activation phenotype decreases alpha-synuclein pathology in an in vivo model of Parkinson’s Disease-related alpha-synucleinopathy and increases astrocytic protein uptake and degradation in vitro. This study therefore provides insight into astrocyte function and could elucidate novel regulatory mechanisms that are candidates for therapeutic manipulation through modulating REV-ERB activity.
Published in
REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function
Nadarajah CJ, Li MY, Quillin EI et al. · Proceedings of the National Academy of Sciences of the United States of America 2026 · PMID 41615759 · doi:10.1073/pnas.2511093123
This dataset
Open GSE293026 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 GSE293026_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 PRJNA1242371 and SRA study SRP573441. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41615759) ↗
Study design
6 conditions, mostly with about 5 replicates each
Cortex, CAG-Cre Neg RVAff RVBff, ×6 Cortex, CAG-Cre Pos RVAff RVBff, ×5 Cortex, CAG-Cre Neg RVAff, ×5 Cortex, CAG-Cre Neg DBDff, ×4 Cortex, CAG-Cre Pos DBDff, ×3 Cortex, CAG-Cre Pos, RVAff, ×3

Supports a between-group comparison across 26 samples.

How we read this: 6 replicated groups read from 26 sample titles; they account for 26 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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