The Elusive S Cells: Reevaluating Enteroendocrine Cell Classification

Abstract The nomenclature of enteroendocrine cells (EECs), established in 1977, applies the ”one cell - one hormone” dogma, which distinguishes subpopulations based on the secretion of a specific hormone. These hormone-specific subpopulations include S cells for secretin, K cells for glucose-dependent insulinotropic polypeptide, N cells producing neurotensin (NTS), I cells producing cholecystokinin (CCK), D cells producing somatostatin (SST), and others. Our study challenges this doctrine, showing that the expression of certain hormones is not confined to their designated cell type. Moreover, our findings do not confirm the presence of S cells or any cell population that exhibits significantly elevated secretin expression compared to other cell populations, despite the common attribution of secretin to S cells in existing literature. Instead, our investigation indicates that secretin is not synthesized by S cells; rather, its secretion is realized jointly by other enteroendocrine subpopulations.