GEO series

6-phosphogluconate dehydrogenase blockade in T Cells mitigates acute graft-versus-host disease while preserving graft-versus-tumor activity

GSE289995 Mus musculus (mouse) Single-cell RNA-seq 2 samples Submitted 2025/04/30 Platform GPL19057

At a glance

Single-cell RNA-seq · mouse · 2 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 2 samples
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)

T cells undergo significant metabolic reprogramming after allogeneic hematopoietic cell transplantation (allo-HCT). However, the influence of metabolic pathway reprogramming on altering the severity and mortality of acute graft-versus-host disease (aGvHD), a critical allo-HCT complication, remains unclear.

Read the full summary ↓

Through single-cell RNA sequencing (scRNA-seq) of allogeneic T cells isolated from the spleen of GvHD mice, we uncovered that 6-phosphogluconate dehydrogenase (6PGD), the second major rate-limiting enzyme in the oxidative pentose phosphate pathway, is upregulated and activated during allo-HCT. Clinical and histopathological analyses revealed that 6PGD deficiency in donor T cells significantly mitigates aGvHD severity and mortality in murine models of acute GvHD. An in vitro assay using murine and human T cells and an in vivo murine GvHD model showed that in the absence of an intact 6PGD pathway, donor T cell proliferation was reduced. Metabolic analyses confirmed that blocking 6PGD activity shifted T cell metabolism from glycolysis to oxidative phosphorylation (OXPHOS), as evidenced by isotope-labeled metabolic tracing and Seahorse assays. Pharmacological inhibition of 6PGD with 6-aminonicotinamide (6AN) demonstrated similar efficacy as the infusion of donor 6PGD deficient T cells in reducing aGvHD severity in allogeneic aGvHD and humanized xenogeneic GvHD models. Importantly, 6PGD inhibition preserved the graft-versus-tumor (GvT) effect by promoting the generation of a small subset of effector T cells with potent anti-tumor activity. From these findings we propose 6PGD as a promising therapeutic target for alleviating aGVHD the beneficial GvT effects.

This dataset

Open GSE289995 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 GSE289995_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1225717 and SRA study SRP565105. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 2 more — browse all 2 samples with per-sample file links →

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