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Targeting the histone methyltransferase DOT1L rewires CD8 T cells and enhances their intrinsic cytotoxic activity towards tumor cells [RNAseq_WT_KO_DMSO_EPZ]

GSE282854 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2025/11/03 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 4 × CD8, DMSO, 8days, biol vs 4 × CD8, EPZ, 8days, biol vs 3 × CD8, DOT1L-KO, 8days, biol vs 3 × CD8, DOT1L-WT, 8days, biolGroups 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
Histone methyltransferase DOT1L maintains cell state and restricts cytotoxic potential of CD8 T cellsScience advances · 2025
Summary (written by the submitters)
Insights into the epigenetic mechanisms of CD8 T cell differentiation are delivering novel opportunities for modulating fate decisions and immune responses. The histone methyltransferase DOT1L is emerging as a central epigenetic regulator in immune cells. However, its cell-intrinsic role in CD8 T cell programming remains unclear as positive as well as negative roles have been ascribed to DOT1L.
Read the full summary ↓
Here, we determined the cell-intrinsic role of DOT1L in mouse CD8 T cells using conditional ablation. In contrast to deletion of Dot1L early in the T cell lineage, conditional ablation of Dot1L in isolated mature CD8 T cells in vitro did not compromise the in vivo proliferative capacity and anti-tumor reactivity. In vitro, Dot1L knock-out CD8 T cells showed accelerated and enhanced antigen-specific cytotoxic activity towards tumor cells. Mechanistically, transcriptome and proteome profiling revealed that loss of DOT1L results in an altered cell-identity program with loss of T-cell and gain of NK-cell features. This role of DOT1L was linked to its catalytic activity since treatment with specific DOT1L inhibitors phenocopied genetic deletion of Dot1L. Our findings show that ablation of DOT1L activity is well-tolerated in mature CD8 T cells, rewires their cell identity in a tunable way towards the NK-cell lineage and enhances their cytolytic activity cell intrinsically.
Published in
Histone methyltransferase DOT1L maintains cell state and restricts cytotoxic potential of CD8 T cells
Malik M, de Leeuw WJ, Aslam MA et al. · Science advances 2025 · PMID 41385642 · doi:10.1126/sciadv.adw1289
This dataset
Open GSE282854 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 GSE282854_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 PRJNA1190862 and SRA study SRP547663. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41385642) ↗
Study design
4 × CD8, DMSO, 8days, biol vs 4 × CD8, EPZ, 8days, biol vs 3 × CD8, DOT1L-KO, 8days, biol vs 3 × CD8, DOT1L-WT, 8days, biol

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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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