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Metabolically and epigenetically reprogrammed splenic TRNP1hiCD8+ T cells exacerbate liver fibrosis

GSE299225 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 13 samples Submitted 2026/04/30 Platform GPL34290
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 13 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
13 samples: 3 × ND, Splenic CD8+ T cells, H3K27me3， vs 3 × CDAHFD, Splenic CD8+ T cells, H3K27me3, vs 3 × ND, Splenic CD8+ T cells, H3K27ac, vs 3 × CDAHFD, Splenic CD8+ T cells, H3K27ac,Groups 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.
Summary (written by the submitters)
MASLD, especially its severe form MASH, progresses to liver fibrosis, leading to cirrhosis and liver cancer. The crosstalk between spleen and liver in MASLD/MASH progression remains poorly understood. Here, we find the enlarged spleens in MASLD patients, and the induced TRNP1hiCD8+ T cells in the spleens of MASLD/MASH mouse models and confirmed in MASLD patients, with pro-fibrotic property by secreting INSR-α.
Read the full summary ↓
Mechanistically, demethylated DNA and H3K27me3, increased H3K27ac, together with bolstered enhancer-promoter contact, synergistically reorganized chromatin topologically associating domains spatially to initiate the expression of transcription factor TRNP1 in splenic CD8+ T cells. TRNP1 then transcriptionally activates the expression of FURIN and CTSD, promoting the maturation and ectodomain shedding of INSR-α thereby facilitating its secretion to activate hepatic stellate cells. In vivo blockade of INSR-α using neutralizing antibodies alleviates MASLD/MASH-induced liver fibrosis. Therefore, this study reveals splenic TRNP1hiCD8+ T cells with pro-fibrotic property and suggests a potential anti-fibrotic strategy.
This dataset
Open GSE299225 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE299225_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1273103 and SRA study SRP590436. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × ND, Splenic CD8+ T cells, H3K27me3， vs 3 × CDAHFD, Splenic CD8+ T cells, H3K27me3, vs 3 × ND, Splenic CD8+ T cells, H3K27ac, vs 3 × CDAHFD, Splenic CD8+ T cells, H3K27ac,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 13 sample titles; they account for 12 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
Datasets on a similar topic

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