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25-hydroxycholesterol mediates brain cytokine production and neutrophil infiltration in a mouse model of LPS-induced neuroinflammation.

GSE250279 Mus musculus (mouse) RNA-seq (gene expression) 40 samples Submitted 2024/12/21 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 40 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
40 samples: 40 samples, each with a distinct title — no replicated groupsGroups 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
25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammationJournal of neuroinflammation · 2024
Summary (written by the submitters)
Neuroinflammation has been implicated in the pathogenesis of several neurologic and psychiatric disorders. Microglia are key drivers of neuroinflammation and in response to different inflammatory stimuli overexpress a proinflammatory signature of genes. Among these, Ch25h is a gene overexpressed in brain tissue from Alzheimer’s disease as well as various mouse models of neuroinflammation.
Read the full summary ↓
Ch25h encodes cholesterol 25-hydroxylase, an enzyme that hydroxylates cholesterol to form 25-hydroxycholesterol (25HC). 25HC, an immune-oxysterol primarily produced by activated microglia, is further metabolized to 7,25-dihydroxycholesterol, which is a potent chemoattractant for leukocytes. We have also previously shown that 25HC increases production and secretion of the proinflammatory cytokine, IL-1, by mouse microglia treated with lipopolysaccharide (LPS). In the present study, wildtype (WT) and Ch25h-knockout (CKO) mice were peripherally administered LPS to induce an inflammatory state in the brain. In LPS-treated WT mice, Ch25h expression and 25HC levels increased in brain relative to vehicle-treated WT mice. Interestingly, 25HC levels were significantly higher in LPS-treated WT female compared to male mice. Activation of microglia and astrocytes in response to systemic LPS was suppressed in CKO mice relative to WT mice. Proinflammatory cytokine production and intra-parenchymal infiltration of neutrophils strongly correlated with brain 25HC levels and were significantly lower in CKO compared to WT mice. Overall, our results show that 25HC mediates a sex-specific proinflammatory response in the brain characterized by activation of both microglia and astrocytes but also by neutrophil migration into the brain parenchyma presumably due to 7,25-diHC produced from 25HC.
Published in
25-hydroxycholesterol promotes brain cytokine production and leukocyte infiltration in a mouse model of lipopolysaccharide-induced neuroinflammation
Romero J, Toral-Rios D, Yu J et al. · Journal of neuroinflammation 2024 · PMID 39369253 · doi:10.1186/s12974-024-03233-1
This dataset
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.

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 GSE250279_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1053288 and SRA study SRP478246. Searching any of these in the dataset finder brings you back here.

Study design
40 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 40 sample titles: 40 distinct titles with little repetition. 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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