GEO series

Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy

GSE279983 Mus musculus (mouse) DNA methylation 20 samples Submitted 2025/06/17 Platform GPL24676Platform GPL24247

At a glance

DNA methylation · mouse · 20 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Mus musculus (mouse)
Samples: 20 samples: 7 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: Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacyNature immunology · 2025

Summary (written by the submitters)

CD4+ T cells differentiate into various subsets, including T helper 1 (Th1), Th2, Th9, Th17, and regulatory T cells, which are essential in immune responses and cancer immunotherapy. However, the role of RNA N6-methyladenosine (m6A) modification in this differentiation remains unclear. Here, we demonstrate that YTHDF2, a key m6A reader protein known to destabilize m6A-modified mRNA, negatively regulates Th9 cell differentiation.

Read the full summary ↓

Ablation of Ythdf2 in both mouse and human naïve CD4+ T cells significantly promotes Th9 differentiation by stabilizing Gata3 and Smad3 mRNA under IL-4 and TGF-β signaling. Ythdf2-deficient Th9 cells produce higher levels of IL-9 and IL-21, leading to increased tumor infiltration and cytotoxicity by CD8+ T and NK cells, thereby improving antitumor activity versus wild-type Th9 cells. Moreover, YTHDF2 depletion in CAR-Th9 cells enhances immune activation, reduces terminal differentiation, and augments antitumor efficacy. Targeting YTHDF2 thus represents a promising strategy for enhancing Th9 and CAR-Th9 cell-based cancer immunotherapies.

Published in

Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy

Xiao S, Duan S, Hong Y et al. · Nature immunology 2025 · PMID 40826275 · doi:10.1038/s41590-025-02235-2

This dataset

Open GSE279983 in finder → Find more 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 GSE279983_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 beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1175660 and SRA study SRP539939. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40826275) ↗

Study design

7 conditions, mostly in triplicate

WT_Th9_MeRIP ×3 KO_Th9_MeRIP ×3 m_WT_Th9 ×3 m_KO_Th9 ×3 H_WT_Th9 ×3 H_KO_Th9 ×3 Th9_RIP ×2

Supports a between-group comparison across 20 samples.

How we read this: 7 replicated groups read from 20 sample titles; they account for 20 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

GSM8585153 WT_Th9_MeRIP1 WT_Th9_MeRIP
GSM8585154 WT_Th9_MeRIP2 WT_Th9_MeRIP
GSM8585155 WT_Th9_MeRIP3 WT_Th9_MeRIP
GSM8585156 KO_Th9_MeRIP1 KO_Th9_MeRIP
GSM8585157 KO_Th9_MeRIP2 KO_Th9_MeRIP
GSM8585158 KO_Th9_MeRIP3 KO_Th9_MeRIP
GSM8585159 Th9_RIP1 Th9_RIP
GSM8585160 Th9_RIP2 Th9_RIP
GSM8585161 m_WT_Th9_1 m_WT_Th9
GSM8585162 m_WT_Th9_2 m_WT_Th9
GSM8585163 m_WT_Th9_3 m_WT_Th9
GSM8585164 m_KO_Th9_1 m_KO_Th9
GSM8585165 m_KO_Th9_2 m_KO_Th9
GSM8585166 m_KO_Th9_3 m_KO_Th9
GSM8585167 H_WT_Th9_1 H_WT_Th9
GSM8585168 H_WT_Th9_2 H_WT_Th9
GSM8585169 H_WT_Th9_3 H_WT_Th9
GSM8585170 H_KO_Th9_1 H_KO_Th9
GSM8585171 H_KO_Th9_2 H_KO_Th9
GSM8585172 H_KO_Th9_3 H_KO_Th9

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