GEO series

Exploring the Mechanism of SETDB1 in Regulating Neuroinflammation and Anxiety-Depression-like Behaviors [RNA-seq]

GSE275353 Mus musculus (mouse) Single-nucleus RNA-seq 19 samples Submitted 2026/04/04 Platform GPL28457Platform GPL30215Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 19 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 19 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: SETDB1 modulates neuroinflammation in the mouse cortex by regulating neuronal P2rx7 expressionMolecular psychiatry · 2026

Summary (written by the submitters)

Depression is a globally prevalent disabling mental illness with serious social hazards. Previous studies suggest that neuroinflammation plays an important role in the pathogenesis of depression, but the underlying mechanism remains elusive. Endogenous retrovirus (ERVs) is a type of transposable elements (TEs), consists around 8% of human genome but are mostly silenced in vivo.

Read the full summary ↓

Repressive histone modifications H3K9me3 mediated by the methyltransferase SETDB1 plays a key role in maintaining silencing of ERVs. In this study, we constructed Setdb1-CK-cKO (KO) transgenic mice. Behavioral tests showed that the KO mice exhibited anxiety-depression-like behaviors compared to wild type (WT). Cortex snRNA-seq analysis revealed significant changes in astrocytes in addition to excitatory neurons, with the emergence of a new sub cluster of astrocytes in the KO whose transcriptional profile exhibited specific ERVs activation. We observed a large number of GFAP-positive cells in the KO cortex and striatum by Immunostaining, suggesting reactive astrogliosis. Transcriptomic analysis of astrocytes revealed significant upregulation of genes associated with inflammation in the KO cortex, including multiple chemokine genes. To investigate the potential molecular mechanism underlying "endogenous" neuroinflammation in KO mice, we focused on the purinergic receptor P2X7R, which has been reported to play an important role in mediating neuroinflammation and emotional behaviors. Most importantly, we found that the expression of P2rx7 was significantly upregulated in the KO neuron. We applied multiple epigenomic methods (RNA-seq, ATAC-seq, H3K9me3 ChIP-seq) to analyze in detail the molecular mechanism by which SETDB1 regulates the P2rx7 gene expression, and identified a novel enhancer fragment, mE1. We further constructed a SETDB1 knockout human 293T cell line and examined chromatin accessibility by ATAC-seq. We found a regulatory fragment hE1 with enhancer activity, which was present at a similar location in the human P2RX7 locus, suggesting that this mechanism is conserved between human and mouse. Knockout of P2X7R effectively ameliorated neuroinflammation and partially alleviated neuronal dysfunction as well as behaviors in Setdb1-CK-cKO mice.

Published in

SETDB1 modulates neuroinflammation in the mouse cortex by regulating neuronal P2rx7 expression

Zhu Y, Liao L, Liu X et al. · Molecular psychiatry 2026 · PMID 41935187 · doi:10.1038/s41380-026-03584-6

This dataset

Open GSE275353 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 GSE275353_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1150525 and SRA study SRP527757. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41935187) ↗

Study design

7 conditions, mostly in triplicate

Neuron_WT_RNA ×3 Neuron_KO_RNA ×3 Cortex_WT_RNA ×3 Cortex_KO_RNA ×3 Cortex_DKO_RNA ×3 Astrocyte_WT_RNA ×2 Astrocyte_KO_RNA ×2

Supports a between-group comparison across 19 samples.

How we read this: 7 replicated groups read from 19 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

GSM8475471 Astrocyte_WT_RNA_Rep1 Astrocyte_WT_RNA
GSM8475472 Astrocyte_WT_RNA_Rep2 Astrocyte_WT_RNA
GSM8475473 Astrocyte_KO_RNA_Rep1 Astrocyte_KO_RNA
GSM8475474 Astrocyte_KO_RNA_Rep2 Astrocyte_KO_RNA
GSM8475475 Neuron_WT_RNA_Rep1 Neuron_WT_RNA
GSM8475476 Neuron_WT_RNA_Rep2 Neuron_WT_RNA
GSM8475477 Neuron_WT_RNA_Rep3 Neuron_WT_RNA
GSM8475478 Neuron_KO_RNA_Rep1 Neuron_KO_RNA
GSM8475479 Neuron_KO_RNA_Rep2 Neuron_KO_RNA
GSM8475480 Neuron_KO_RNA_Rep3 Neuron_KO_RNA
GSM8475481 Cortex_WT_RNA_Rep1 Cortex_WT_RNA
GSM8475482 Cortex_WT_RNA_Rep2 Cortex_WT_RNA
GSM8475483 Cortex_WT_RNA_Rep3 Cortex_WT_RNA
GSM8475484 Cortex_KO_RNA_Rep1 Cortex_KO_RNA
GSM8475485 Cortex_KO_RNA_Rep2 Cortex_KO_RNA
GSM8475486 Cortex_KO_RNA_Rep3 Cortex_KO_RNA
GSM8475487 Cortex_DKO_RNA_Rep1 Cortex_DKO_RNA
GSM8475488 Cortex_DKO_RNA_Rep2 Cortex_DKO_RNA
GSM8475489 Cortex_DKO_RNA_Rep3 Cortex_DKO_RNA

Datasets on a similar topic

GSE310141 Microglial reactivity and neuroinflammation-driven in motivational behaviors are regulated by Orai1 channels 67 samples shares neuroinflammation, behaviors
GSE325918 Nuclear receptor Nur77 resolves the inflammatory response of macrophages primarily by regulating expression of AP-1 transcription factors and their target genes [RNA-seq] 32 samples shares regulating, rna-seq
GSE271650 Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes [bulk RNA-seq] 18 samples shares neuroinflammation, rna-seq
GSE297349 CRISPR-Cas9 Screening Reveals Microproteins Regulating Adipocyte Proliferation and Lipid Metabolism [RNA-seq] 18 samples shares regulating, rna-seq
GSE239423 The tumor intrinsic role of the m6A reader YTHDF2 in regulating immune evasion [RNA-seq] 16 samples shares regulating, rna-seq
GSE248443 RNA helicase DDX5 maintains cardiac function by regulating CamkIIδ alternative splicing [RNA-seq] 12 samples shares regulating, rna-seq
GSE287862 Secreted neurofilament light chain (NfL) after neuronal damage induces myeloid cell activation and neuroinflammation [bulkRNA-Seq] 12 samples shares neuroinflammation, rna-seq
GSE304155 HE4 regulates anticancer immune evasion by upregulating PD-L1 expression on macrophages through the IFN-γR-STAT3 axis [LLC tumors, scRNA-seq] 6 samples shares regulating, rna-seq

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.