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Comprehensive mapping of epigenetic events during the T-follicular helper-to-T-regulatory type-1 transdifferentiation pathway reveal a global poised state

GSE248152 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 31 samples Submitted 2024/11/07 Platform GPL24247Platform GPL17021
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 31 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
31 samples: 6 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
T-follicular helper cells are epigenetically poised to transdifferentiate into T-regulatory type 1 cellseLife · 2024
Summary (written by the submitters)
Chronic antigenic stimulation can trigger the formation of IL-10-producing T-regulatory type 1 (TR1) cells in vivo. We have recently shown that T follicular helper cells are precursors of TR1 cells and that the TFH-to-TR1 cell transdifferentiation process is underpinned by the progressive loss and acquision of opposing transcription factor gene expression programs that evolve through at least one transitional cell stage.
Read the full summary ↓
Through a combination of wide-ranging bulk and single-cell transcriptional and epigenetic studies, here we demonstrate that TFH cells are epigenetically poised to differentiate into TR1 cells. Specifically, we find that the TFH-to-TR1 cell transition is accompanied by a significant reduction of the open chromatin regions (OCRs) found in TFH cells. However, the OCRs shared by TR1-like and TFH cells have a remarkably similar distribution of H3K27ac-marked active enhancers. Whereas the DNA regions that overlap these active enhancers are closed and hyper-methylated in conventional T cells, they are hypo-methylated in both TFH and TR1-like cells, even in genes silent in TFH cells, such as Il10. Furthermore, these enhancers are enriched for binding sites for the TFH and TR1-associated transcription factors (TFs) TOX-2, IRF4 and c-Maf. These data suggest that TFH cells are epigenetically poised to become TR1 cells, and that sustained TCR ligation-induced chromatin remodeling coupled to the acquisition of an alternative transcription factor expression profile are sufficient to drive their transdifferentiation into TR1 cells.
Published in
T-follicular helper cells are epigenetically poised to transdifferentiate into T-regulatory type 1 cells
Garnica J, Sole P, Yamanouchi J et al. · eLife 2024 · PMID 39576679 · doi:10.7554/eLife.97665
This dataset
Open GSE248152 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE248152_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 PRJNA1041837 and SRA study SRP472606. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39576679) ↗
Study design
6 conditions, mostly in triplicate
ATACseq Tet+, ×4 ATACseq vaccination-induced TFH, ×3 ATACseq Th0, ×3 Methylome Tet+, ×3 Methylome vaccination-induced TFH, ×3 Methylome Tconv, ×3 ChIPseq H3K27Ac, Tet+ ×1 ChIPseq H3K27Ac, vaccination-induced TFH ×1 +10 more

Supports a between-group comparison across 19 samples.

How we read this: 6 replicated groups read from 31 sample titles; they account for 19 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
Datasets on a similar topic

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