Repository logo

A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium.

Change log


Adriaenssens, Alice 
Lam, Brian Yee Hong 
Billing, Lawrence 
Skeffington, Katie 
Sewing, Sabine 


The stomach epithelium contains a myriad of enteroendocrine cells that modulate a range of physiological functions, including postprandial secretion of regulatory peptides, gastric motility, and nutrient absorption. Somatostatin (SST)-producing D-cells are present in the oxyntic and pyloric regions of the stomach, and provide a tonic inhibitory tone that regulates activity of neighboring enteroendocrine cells and gastric acid secretion. Cellular mechanisms underlying the effects of regulatory factors on gastric D-cells are poorly defined due to problems in identifying primary D-cells, and uncertainty remains about which stimuli influence D-cells directly. In this study, we introduce a transgenic mouse line, SST-Cre, which upon crossing with Cre reporter strains, facilitates the identification and purification of gastric D-cells, or cell-specific expression of genetically encoded calcium indicators. Populations of D-cells from the gastric antrum and corpus were isolated and analyzed by RNA sequencing and quantitative RT-PCR. The expression of hormones, hormone receptors, neurotransmitter receptors, and nutrient receptors was quantified. Pyy, Gipr, Chrm4, Calcrl, Taar1, and Casr were identified as genes that are highly enriched in D-cells compared with SST-negative cells. Hormone secretion assays performed in mixed gastric epithelial cultures confirmed that SST secretion is regulated by incretin hormones, cholecystokinin, acetylcholine, vasoactive intestinal polypeptide, calcitonin gene-related polypeptide, oligopetides, and trace amines. Cholecystokinin and oligopeptides elicited increases in intracellular calcium in single-cell imaging experiments performed using cultured D-cells. Our data provide the first transcriptomic analysis and functional characterization of gastric D-cells, and identify regulatory pathways that underlie the direct detection of stimuli by this cell type.



Animals, Calcium, Cells, Cultured, Epithelial Cells, Female, Gastric Mucosa, Hormones, Luminescent Proteins, Male, Mice, Inbred NOD, Mice, Transgenic, Microscopy, Fluorescence, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, RNA, Single-Cell Analysis, Somatostatin, Somatostatin-Secreting Cells, Stomach, Transcriptome

Journal Title


Conference Name

Journal ISSN


Volume Title


The Endocrine Society
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/5/B)
Medical Research Council (MC_PC_12012)
This work was supported by the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z) and the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3).