← BioTransfer GEO Dataset Finder
GEO series

Osr2 functions as a mechanical checkpoint to augment CD8+ T cell exhaustion [YODA1_vs_DMSO_ATAC_CD8]

GSE223157 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 12 samples Submitted 2024/05/14 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 12 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
12 samples: 3 × ATAC_WT_DMSO vs 3 × ATAC_WT_Yoda1 vs 3 × ATAC_Piezo1-KO_DMSO vs 3 × ATAC_Piezo1-KO_Yoda1Groups 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.
Summary (written by the submitters)
The alteration in extracellular matrix (ECM) architecture and stiffness becomes one of the hallmarks of cancer. Whether the mechanical property of ECM contributes to the functionality of CD8+ T cells, a key component of anti-tumor response, remains largely unknown. Here we report that mechanical stress drives T cell exhaustion program via Osr2, a transcription factor that had been poorly investigated in T cells.
Read the full summary ↓
Osr2 is highly and selectively induced in CD8+ T cells when encountering stiff matrix or mechanical force signaling (MFS). Integrated genetic and multi-omics analyses reveals that Osr2 is enriched in the terminal exhausted tumor infiltrating lymphocytes and its expression is modulated by the combined TCR and MFS mediated by Piezo1/Calcium/CREB axis. Importantly, depletion of Piezo1 or Osr2 alleviates T cell exhaustion, which is associated with enhanced anti-tumor immunity mediated by antigen specific T cells or CAR-T cells in solid tumor models. On the contrary, forced Osr2 expression in CD8+ T cells augment their exhaustion and dampens tumor control. In agreement with these observations, high Osr2 expression is correlated with poor prognosis in multiple human malignancies. Mechanistically, Osr2 recruits HDAC3, which in turn establishes epigenetic reprogramming to suppress cytotoxic genes expression and to promote CD8+T cell exhaustion. Thus, our results unravel a mechanical signaling cascade centered by Osr2 that serves as a key driver for CD8+ T cell exhaustion and suggest that mechanical checkpoints could be promising targets for cancer immunotherapy.
This dataset
Open GSE223157 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 GSE223157_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 PRJNA925157 and SRA study SRP418124. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × ATAC_WT_DMSO vs 3 × ATAC_WT_Yoda1 vs 3 × ATAC_Piezo1-KO_DMSO vs 3 × ATAC_Piezo1-KO_Yoda1

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

Search all mouse ChIP / ATAC / CUT&Tag datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.