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Arid1a mediates cell recovery upon gastric injury to prevent tumorigenesis [Multiome]

GSE269928 Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2026/06/30 Platform GPL24247
Summary
When tissues and organs are damaged, they undergo a reversible regenerative response. Since it often activates oncogenic signaling pathways, recovery after regeneration must be precisely regulated. However, its underlying mechanisms and relationship with cancer remain unclear. The stomach is constantly exposed to environmental damages such as H. pylori infection and ulcer, and undergoes an evolutionally conserved, regenerative response called spasmolytic polypeptide-expressing metaplasia (SPEM). Although this process is highly reversible, occurring in precancerous lesions, the epigenetic regulation underlying SPEM is unknown. Our single-cell chromatin and gene expression analysis defines cell fate and state dynamics in homeostasis, regeneration and recovery. Upon injury, gastric epithelial cells rapidly induce SPEM gene expression under accessible chromatin, while losing the expression and accessibility of differentiation genes. Strikingly, when Arid1a, the second most mutated gastric cancer gene, is deleted in regeneration, it abolishes cell recovery. By analyzing histone modification and chromatin accessibility, as well as mapping the binding sites of ARID1A and BRG1, we demonstrate they promote recovery through the regulation of enhancer activity. Notably, failed recovery by Arid1a loss in combination with Trp53 deletion is sufficient to induce cancer initiation and invasion, providing key insight into the mechanistic relationship between tissue recovery after regeneration and cancer.
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Direct links to NCBI, no account and no request form: the whole study as GSE269928_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 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 PRJNA1124131 and SRA study SRP514045. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
8 conditions, each sampled once — no replicated groups
stomach, day7, GEX, ×2

Supports a case/control comparison: 2 samples read as cases, 2 as controls.

Read from 9 sample titles: 8 distinct titles with little repetition. Check it against the sample list below before relying on it.

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