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Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma

GSE279041 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/10/16 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 4 × Mouse CD8+ T cells, empty vector retroviral transduction vs 4 × Mouse CD8+ T cells, PDK1 retroviral transduction vs 4 × Mouse CD8+ T cells, PDP1 retroviral transductionGroups 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
Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphomaJCI insight · 2025
Summary (written by the submitters)
T cells rely on different metabolic pathways to differentiate into effector or memory cells, and metabolic intervention is a promising strategy to optimize T cell function for immunotherapy. Pyruvate dehydrogenase (PDH) is a nexus between glycolytic and mitochondrial metabolism, regulating pyruvate conversion either to lactate or acetyl-CoA.
Read the full summary ↓
Here, we retrovirally transduced pyruvate dehydrogenase kinase 1 (PDK1) or pyruvate dehydrogenase phosphatase 1 (PDP1), which control PDH activity, into CD8+ T cells to test effects on T cell function. Although PDK1 and PDP1 were expected to influence PDH in opposing directions, by several criteria they induced similar changes relative to control T cells. Seahorse metabolic flux assays showed both groups exhibited increased glycolysis and oxidative phosphorylation. Both groups had improved primary and memory recall responses following infection with murine gammaherpesvirus-68 (MHV-68). However, metabolomics using labeled fuels indicated differential usage of key fuels by metabolic pathways. Importantly, after B cell lymphoma challenge the engineered CD8+ T cells produced smaller effector populations in the tumor, resulting in larger tumors and poorer survival compared with control cells. Overall, this study indicates that PDK1 and PDP1 both enhance metabolic capacity, but the context of the antigenic challenge significantly influences the consequences for T cell function.
Published in
Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma
Kang T, Usherwood YK, Reisz JA et al. · JCI insight 2025 · PMID 40857407 · doi:10.1172/jci.insight.187680
This dataset
Open GSE279041 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 GSE279041_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 PRJNA1170222 and SRA study SRP537149. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40857407) ↗
Study design
4 × Mouse CD8+ T cells, empty vector retroviral transduction vs 4 × Mouse CD8+ T cells, PDK1 retroviral transduction vs 4 × Mouse CD8+ T cells, PDP1 retroviral transduction

Supports a between-group comparison across 12 samples.

How we read this: 3 replicated groups read from 12 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
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