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Mettl8 programs Tcf1+CXCR5+ T cells in autoimmune disease and tumor by mediating Tcf1 mRNA m3C modification and Tcf1-bound chromatin loops

GSE249068 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 62 samples Submitted 2026/03/07 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 62 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
62 samples: 15 conditions, mostly in triplicateGroups 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 Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunityThe Journal of experimental medicine · 2026
Summary (written by the submitters)
In the tumor microenvironment (TME), the active tertiary lymphoid structure (TLS) plays a crucial role in fostering the reactivation of naïve or memory cells, leading to the expansion of effector cells. However, an excessive reinvigoration of T cells can result in autoimmune-like diseases, such as those observed in immune checkpoint blockade (ICB) therapy.
Read the full summary ↓
Here, we have identified that the gene encoding RNA methyltransferase Mettl8 is highly expressed in inflammatory CD4+ CXCL13+ TFH cells of autoimmune patients. Surprisingly, the genetic deletion of Mettl8 in mice resulted in a reduced autoimmune phenotype in helper CD4 cells and slowed tumor growth through increased activation/effector response in CD8+ T cells. Mechanistically, Mettl8 is found to imprint m3C modification, stabilizing Tcf1 mRNA, and simultaneously interacts with Tcf1 protein to co-bind specific genome loops for genomic reorganization, as revealed by Hi-C analysis. These findings suggest that targeting Mettl8 promotes antitumor immunity while preventing the occurrence of autoimmune diseases. Notably, pharmacological inhibition of sumoylation-stabilizing Mettl8 protein has shown efficacy in compromising autoimmune CXCL13+ TFH specialization and function. In conclusion, these findings underscore the dual regulatory elements of the Mettl8-Tcf1 complex as a promising target for tumor immunotherapy, offering protection against autoimmune diseases.
Published in
Targeting Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunity
Song J, Cui D, Wang J et al. · The Journal of experimental medicine 2026 · PMID 41891923 · doi:10.1084/jem.20250424
This dataset
Open GSE249068 in finder → Find more mouse 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 GSE249068_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 PRJNA1047113 and SRA study SRP475190. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41891923) ↗
Study design
15 conditions, mostly in triplicate
CD8_RNA_WT ×4 CD8_RNA_KO ×4 TFH-_KO ×4 Tpex_RNA_WT ×3 Tpex_RNA_KO ×3 intTex_RNA_WT ×3 intTex_RNA_KO ×3 Tex_RNA_WT ×3 +37 more

Supports a between-group comparison across 43 samples.

How we read this: 15 replicated groups read from 73 sample titles; they account for 43 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

+ 22 more — browse all 62 samples with per-sample file links →

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