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We integrated epigenomic\u2010transcriptomic analysis of human GIM and normal tissues, validated targets via dual\u2010luciferase assay, and mapped cellular heterogeneity by single\u2010cell RNA sequencing of patient\u2010derived gastric organoids. Functional validation using organoids included STAT3 knockdown assessed by qRT\u2010PCR and immunofluorescence. STAT3 was identified as a top regulator of hypomethylated, upregulated genes in GIM and directly transactivated CCND2. Single\u2010cell analysis revealed a dominant proliferative \u201cCycling GIM\u2010precursor\u201d population co\u2010expressing STAT3\/CCND2. STAT3 knockdown reduced CCND2 and intestinal markers (CDX2, MUC2) in GIM organoids. 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