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Transient high fat diet causes persistent susceptibility to ferroptosis in CD8 T cells [Ex_vivo_RNAseq]

GSE276598 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2026/03/06 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 × CD8, normal diet fed mice, vs 6 × CD8, switched diet fed mice, vs 6 × CD8, high fat diet fed mice,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.
Paper
Purine salvage pathway protects CD8(+) T cells from metabolic stressNature immunology · 2026
Summary (written by the submitters)
Chronic metabolic stress impacts the immune cell function, increasing the incidence of autoimmune diseases and cancers. Whether past history of a high fat diet (HFD) leads to immune dysfunction is less understood. Moreover, whether factors other than persistent epigenetic changes would impact on the immune function remain unknown. We find that even a transient exposure to HFD causes persistent metabolome changes and long-term vulnerability of CD8 T cells to oxidative stress.
Read the full summary ↓
The past HFD signature of CD8 T cells includes enrichment of lipid species highly susceptible to ferroptosis, and depletion of metabolites with anti-oxidant function. We find that xanthine, through the salvage purine pathway fuels the GTP, which is subsequently converted to tetrahydrobiopterin (BH4) and dihydrobiopterin (BH2). Xanthine-derived biopterins serve as ROS scavengers, rescuing CD8 T cells from activation-induced ferroptosis. Administration of xanthine or BH2 markedly reduces tumor growth in mice transiently fed HFD. Our data uncover that metabolic stress remains tattooed on membrane lipids, generating vulnerability to oxidative stress and ferroptosis, that can be mitigated by purine salvage pathway through the replenishment of guanines and biopterins pools.
Published in
Purine salvage pathway protects CD8(+) T cells from metabolic stress
Tajima M, Hao H, Zhang B et al. · Nature immunology 2026 · PMID 41974963 · doi:10.1038/s41590-026-02491-w
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 GSE276598_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 PRJNA1157898 and SRA study SRP531187. Searching any of these in the dataset finder brings you back here.

Study design
6 × CD8, normal diet fed mice, vs 6 × CD8, switched diet fed mice, vs 6 × CD8, high fat diet fed mice,

Supports a between-group comparison across 18 samples.

How we read this: 3 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
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