GEO series

Hexokinase 2 Exacerbates Mitochondrial Damage, Neuroinflammation, and Lipid accumulation by promoting ACSL4 ISGylation in Sepsis-Associated Encephalopathy

GSE280721 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/04/30 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 4 × S vs 4 × L vs 4 × Sham vs 4 × CLPGroups 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: Hexokinase 2 promotes ISGylation of Acyl-CoA synthetase long-chain family member 4 in sepsis-induced microglia cellsJournal of lipid research · 2025

Summary (written by the submitters)

Metabolic reprogramming is often observed in sepsis-associated encephalopathy (SAE). However, little is known about the aberrant metabolic genes involved in mitochondrial damage, neuroinflammation, and lipid accumulation in microglial cells. Here, we show that hexokinase 2 (HK2) is upregulated and is strongly associated with the inflammatory response and lipid metabolism in lipopolysaccharide-induced BV2 cells.

Read the full summary ↓

Genetic silencing or pharmacological inhibition of HK2 attenuates mitochondrial damage in vitro. Downregulation of HK2 lowered the NOD-like receptor signaling family pyrin domain containing three activations, both in BV2 cells and in the hippocampus of cecal ligation and puncture-induced male septic mice. Moreover, the inhibition of HK2 promoted lipid droplet reduction and activated mammalian target of rapamycin-mediated autophagy. Mechanistically, HK2 knockdown in microglial cells reduced the ISGylation of Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4) during lipid metabolism by interferon-stimulated gene 15 (ISG15). Notably, ISG15 eﬀectively down-regulated the expression of ACSL4 in vitro. Our findings provide new mechanistic insights of HK2 in microglial cells through regulation of ACSL4 ISGylation, suggesting a promising therapeutic strategy for treating SAE by targeting HK2.

Published in

Hexokinase 2 promotes ISGylation of Acyl-CoA synthetase long-chain family member 4 in sepsis-induced microglia cells

Bai G, Ke S, Lu J et al. · Journal of lipid research 2025 · PMID 40086696 · doi:10.1016/j.jlr.2025.100776

This dataset

Open GSE280721 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 GSE280721_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 PRJNA1180095 and SRA study SRP542214. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40086696) ↗

Study design

4 × S vs 4 × L vs 4 × Sham vs 4 × CLP

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM8604865 S1 S
GSM8604866 S2 S
GSM8604867 S3 S
GSM8604868 S4 S
GSM8604869 L1 L
GSM8604870 L2 L
GSM8604871 L3 L
GSM8604872 L4 L
GSM8604873 Sham1 Sham
GSM8604874 Sham2 Sham
GSM8604875 Sham3 Sham
GSM8604876 Sham4 Sham
GSM8604877 CLP1 CLP
GSM8604878 CLP2 CLP
GSM8604879 CLP3 CLP
GSM8604880 CLP4 CLP

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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.