GEO series

Genetic and epigenetic regulation of Treg cell fitness by autism-related chromatin remodeler CHD8

GSE279810 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 18 samples Submitted 2024/12/11 Platform GPL24247

Summary

Chromatin remodeler CHD8 defines a subtype of autism. Its role in regulatory T cells (Tregs) that maintain immune tolerance through suppressing CD4+ and CD8+ effector T cells remain unknown. In this study, we found that Treg-specific CHD8 deletion led to early, fatal inflammatory disorders, due to increased CD4+ and CD8+ effector T cells. CHD8 deletion increased Treg plasticity as evidenced by elevated effector T cell cytokine expression in Tregs. CHIP-seq uncovered that CHD8 binding genes were enriched in PI3K-Akt-mTOR signaling and several other pathways. RNA-seq and ATAC-seq revealed that CHD8 deletion upregulated a number of pathways, notably mTORC1 signaling and its mediated glycolysis that have been reported to promote Treg plasticity. Integrating RNA-seq data with ATAC-seq and/or CHIP-seq data indicates that CHD8 regulates gene expression in either chromatin remodeling- and/or CHD8 binding-dependent or -independent manner. Collectively, our findings suggest that CHD8 plays an important role in maintaining Treg fitness via genetic and epigenetic mechanisms.

Published in

Yang JQ, Wang C, Nayak RC et al. · Cellular & molecular biology letters 2025 · PMID 40155813 · doi:10.1186/s11658-025-00711-z

This dataset

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Direct links to NCBI, no account and no request form: the whole study as GSE279810_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 18 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1174721 and SRA study SRP539361. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40155813) ↗

Study design

7 conditions, mostly in duplicate

1G-CHD8 ×2 2G-CHD8 ×2 1G-IgG ×2 2G-IgG ×2 KO1 ×2 WT ×2 KO2 ×2 Guo-W1 ×1 +3 more

Supports a between-group comparison across 14 samples.

7 replicated groups read from 18 sample titles; they account for 14 of them. Check it against the sample list below before relying on it.

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