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Omics · study · 2026

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

Listed in NCBI GEO

When tissues and organs are damaged, they undergo a reversible regenerative response.

Description

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.

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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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Life Sciences
Inferred from text
Cancer 75%
Provenance · 1 source records, 9 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE26992814 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title