<i>Tff2</i> marks gastric corpus progenitors that give rise to pyloric metaplasia/SPEM following injury

BACKGROUND: Spasmolytic polypeptide-expressing metaplasia (SPEM) arises in the gastric corpus in response to oxyntic atrophy, but its cellular origin and role in gastric cancer remain unclear. OBJECTIVE: To define the cellular origin of SPEM in the gastric corpus and its relationship to gastric dysplasia and cancer progression. DESIGN: activation models were applied. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were performed on human gastric tissues to validate differentiation trajectories. RESULTS: progenitors promoted direct progression to dysplasia through acquisition of stem cell-like properties. In contrast, Kras-mutant SPEM and chief cells failed to progress to dysplasia. Human scRNA-seq and spatial transcriptomics revealed distinct differentiation trajectories from isthmus proliferating cells to SPEM or gastric cancer. CONCLUSIONS: progenitors.