GEO series

Adenosine triggers early astrocyte reactivity that provokes microglial reaction and drives the pathogenesis of sepsis-associated encephalopathy

GSE248275 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2024/06/23 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 18 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: 18 samples: 6 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: Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in miceNature communications · 2024

Summary (written by the submitters)

Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity.

Read the full summary ↓

Specific ablation of astrocytic A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as a novel pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.

Published in

Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice

Guo Q, Gobbo D, Zhao N et al. · Nature communications 2024 · PMID 39068155 · doi:10.1038/s41467-024-50466-y

This dataset

Open GSE248275 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 GSE248275_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 PRJNA1043148 and SRA study SRP473083. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39068155) ↗

Study design

6 conditions, mostly in triplicate

cKO, ip, 0h, ×3 ctl, ip, 0h, ×3 cKO, ip, 6h, ×3 ctl, ip, 6h, ×3 cKO, ip, 24h, ×3 ctl, ip, 24h, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

GSM7910787 cKO, ip, 0h, 1 cKO, ip, 0h,
GSM7910788 cKO, ip, 0h, 2 cKO, ip, 0h,
GSM7910789 cKO, ip, 0h, 3 cKO, ip, 0h,
GSM7910790 ctl, ip, 0h, 1 ctl, ip, 0h,
GSM7910791 ctl, ip, 0h, 2 ctl, ip, 0h,
GSM7910792 ctl, ip, 0h, 3 ctl, ip, 0h,
GSM7910793 cKO, ip, 6h, 4 cKO, ip, 6h,
GSM7910794 cKO, ip, 6h, 5 cKO, ip, 6h,
GSM7910795 cKO, ip, 6h, 6 cKO, ip, 6h,
GSM7910796 ctl, ip, 6h, 4 ctl, ip, 6h,
GSM7910797 ctl, ip, 6h, 5 ctl, ip, 6h,
GSM7910798 ctl, ip, 6h, 6 ctl, ip, 6h,
GSM7910799 cKO, ip, 24h, 4 cKO, ip, 24h,
GSM7910800 cKO, ip, 24h, 5 cKO, ip, 24h,
GSM7910801 cKO, ip, 24h, 6 cKO, ip, 24h,
GSM7910802 ctl, ip, 24h, 4 ctl, ip, 24h,
GSM7910803 ctl, ip, 24h, 5 ctl, ip, 24h,
GSM7910804 ctl, ip, 24h, 6 ctl, ip, 24h,

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GSE310141 Microglial reactivity and neuroinflammation-driven in motivational behaviors are regulated by Orai1 channels 67 samples shares reactivity, microglial
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GSE293026 REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function 26 samples shares reactivity, astrocyte
GSE294133 CLU alleviates Alzheimer’s disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density [RNA-Seq] 19 samples shares reactivity, astrocyte
GSE280721 Hexokinase 2 Exacerbates Mitochondrial Damage, Neuroinflammation, and Lipid accumulation by promoting ACSL4 ISGylation in Sepsis-Associated Encephalopathy 16 samples shares sepsis-associated, encephalopathy
GSE327604 Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer’s disease pathogenesis [RNA-Seq] 12 samples shares pathogenesis, microglial

Search all mouse RNA-seq datasets in GEO →

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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.