GEO series

Heterochromatin-dependent gene silencing controls CD4 T cell response to Treg-mediated suppression [Tmem]

GSE275355 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/11/25 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 4 × Tmem cells, HP1a KO, vs 4 × Tmem cells, HP1g KO, vs 4 × Tmem cells, HP1a WT, vs 4 × Tmem cells, HP1g WT,Groups 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: Heterochromatic gene silencing controls CD4(+) T cell susceptibility to regulatory T cell-mediated suppression in a murine allograft modelNature communications · 2025

Summary (written by the submitters)

The integrity of the organism depends on close and dynamic interactions between conventional and regulatory (Treg) T cells. The extracellular signals and signaling events that regulate this crosstalk have been extensively characterized. However, how conventional T cells translate Treg-dependent immunosuppressive signals at the chromatin level remains largely unknown.

Read the full summary ↓

In differentiating CD4+ T helper (Th) cells, we and others previously reported that transcriptional specificity is largely controlled by heterochromatin-dependent gene silencing. We therefore hypothesized that Treg-mediated T cell suppression could also involve the repressive mark H3K9me3 and the histone-binding factor heterochromatin protein 1 (HP1). Using a bone marrow allograft model, in which graft rejection is coordinated by adoptively-transferred naive CD4+ T cells and can be inhibited by Treg, we show that Treg-dependent suppressive signals indeed mobilize HP1a to repress Th-cell effector genes. Unexpectedly, our screen also revealed that T cells deficient for HP1g or the lysine methyltransferase SUV39H1 are better tolerized than their wild-type counterparts. Mechanistically, our transcriptional and epigenetic profiling identified HP1g as a negative regulator of a network of genes functionally associated with T-cell anergy and exhaustion, including those encoding the transcription factor TOX and the inhibitory receptors PD-1, TIM-3 and LAG-3. In response to T cell receptor engagement, the expression of these immune checkpoints is deregulated in HP1g-deficient cells, thus promoting their better inhibition by Treg. Therefore, we demonstrate that H3K9me3-dependent epigenetic pathways critically regulate Th cell susceptibility to Treg-mediated suppression, and we identify HP1a and HP1g as new epigenetic players whose expression may be manipulated to restore protective immune responses or correct immunopathology, respectively.

Published in

Heterochromatic gene silencing controls CD4(+) T cell susceptibility to regulatory T cell-mediated suppression in a murine allograft model

Noguerol J, Laviolette K, Zahm M et al. · Nature communications 2025 · PMID 39794349 · doi:10.1038/s41467-025-55848-4

This dataset

Open GSE275355 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 GSE275355_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 PRJNA1150523 and SRA study SRP527767. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39794349) ↗

Study design

4 × Tmem cells, HP1a KO, vs 4 × Tmem cells, HP1g KO, vs 4 × Tmem cells, HP1a WT, vs 4 × Tmem cells, HP1g WT,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM8475494 Tmem cells, HP1a KO, R1 Tmem cells, HP1a KO,
GSM8475495 Tmem cells, HP1g KO, R1 Tmem cells, HP1g KO,
GSM8475496 Tmem cells, HP1a KO, R2 Tmem cells, HP1a KO,
GSM8475497 Tmem cells, HP1g KO, R2 Tmem cells, HP1g KO,
GSM8475498 Tmem cells, HP1a KO, R3 Tmem cells, HP1a KO,
GSM8475499 Tmem cells, HP1g KO, R3 Tmem cells, HP1g KO,
GSM8475500 Tmem cells, HP1a KO, R4 Tmem cells, HP1a KO,
GSM8475501 Tmem cells, HP1g KO, R4 Tmem cells, HP1g KO,
GSM8475502 Tmem cells, HP1a WT, R1 Tmem cells, HP1a WT,
GSM8475503 Tmem cells, HP1g WT, R1 Tmem cells, HP1g WT,
GSM8475504 Tmem cells, HP1a WT, R2 Tmem cells, HP1a WT,
GSM8475505 Tmem cells, HP1g WT, R2 Tmem cells, HP1g WT,
GSM8475506 Tmem cells, HP1a WT, R3 Tmem cells, HP1a WT,
GSM8475507 Tmem cells, HP1g WT, R3 Tmem cells, HP1g WT,
GSM8475508 Tmem cells, HP1a WT, R4 Tmem cells, HP1a WT,
GSM8475509 Tmem cells, HP1g WT, R4 Tmem cells, HP1g WT,

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