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Effect of Sin3a deletion on gene expression within FoxP3+ T-regulatory cells

GSE263830 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/06/07 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 3 × Control Treg, female, biol vs 3 × Control Treg, male, biol vs 3 × Sin3a KO Treg, female, biol vs 3 × Sin3a KO Treg, male, biolGroups 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-regulatory cells require Sin3a for stable expression of Foxp3Frontiers in immunology · 2024
Summary (written by the submitters)
Foxp3 (forkhead box protein 3) functions as the master transcriptional regulator of Treg phenotype. Histone deacetylases 1 and 2 (HDAC1/2) contribute to the regulation of FoxP3 expression via interactions with a myriad of co-regulatory factors. While the nuclear scaffolding protein, Sin3a, has been well established as a co-factor of HDAC1/2, its role within FoxP3+ Tregs has not been.
Read the full summary ↓
We analyzed the effects of conditional deletion of Sin3a in Foxp3+ Treg cells using three orthogonal approaches. Deletion of Sin3a from FoxP3+ Tregs resulted in the rapid onset of severe and fatal autoimmunity mirroring the phenotype of Scurfy mice. Numbers of Tregs were greatly reduced, residual Tregs had virtually complete loss of suppressive function, and inducible Treg production was blocked. Mice also showed activation of effector T cells, autoantibody production and widespread tissue injury. Mechanistically, Sin3a deletion resulted in decreased transcription of Foxp3 and other Treg signature genes. The reduction of Foxp3 expression was accompanied by the reduction of TET1 and 3 expression and a complete lack of CpG demethylation of the Foxp3 enhancer region CNS2. In addition, Foxp3 protein stability was impaired and fate mapping studies showed conversion of Tregs to ex-Tregs and increased rates of programmed cell death. Thus, Sin3a plays a critical role in the maintenance of Treg identity and function and is essential for the expression and stability of Foxp3.
Published in
T-regulatory cells require Sin3a for stable expression of Foxp3
Christensen LM, Akimova T, Wang L et al. · Frontiers in immunology 2024 · PMID 39156895 · doi:10.3389/fimmu.2024.1444937
This dataset
Open GSE263830 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 GSE263830_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 PRJNA1099388 and SRA study SRP501334. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39156895) ↗
Study design
3 × Control Treg, female, biol vs 3 × Control Treg, male, biol vs 3 × Sin3a KO Treg, female, biol vs 3 × Sin3a KO Treg, male, biol

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
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