研究人员表示，肠内分泌细胞（EEC）是肠道上皮细胞，通过分泌激素来响应肠内容物，包括调节多种生理过程的促胰岛素激素，如胰高血糖素样肽1（GLP-1）和胃抑制肽（GIP）。激素的释放通过代谢物传感蛋白来调控。低表达、物种间差异以及多种EEC亚型的存在给这些传感器的研究带来了挑战。
研究人员描述了胃EEC的分化，以补充现有的肠道类器官培养方案。CD200被确定为一种泛EEC表面标记物，使其能够对沿胃肠道的原代人类组织进行深度转录组分析。研究人员在22个受体中生成了功能缺失突变，并对类器官进行了配体诱导分泌实验。研究人员阐明了个别人类EEC传感器在激素（包括GLP-1）分泌中的作用。这些传感器可能成为影响食欲、肠道运动、胰岛素敏感性和黏膜免疫的潜在药理学靶点。
附：英文原文
Title: Description and functional validation of human enteroendocrine cell sensors
Author: Joep Beumer, Maarten H. Geurts, Veerle Geurts, Amanda Andersson-Rolf, Ninouk Akkerman, Franziska Vllmy, Daniel Krueger, Georg A. Busslinger, Adriana Martínez-Silgado, Charelle Boot, Fjodor A. Yousef Yengej, Jens Puschhof, Wiline J. Van de Wetering, Kevin Knoops, Carmen López-Iglesias, Peter J. Peters, Judith A. Vivié, Dylan Mooijman, Johan H. van Es, Hans Clevers
Issue&Volume: 2024-10-18
Abstract: Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including the incretins glucagon-like peptide 1 (GLP-1) and gastric inhibitory protein (GIP), which regulate multiple physiological processes. Hormone release is controlled through metabolite-sensing proteins. Low expression, interspecies differences, and the existence of multiple EEC subtypes have posed challenges to the study of these sensors. We describe differentiation of stomach EECs to complement existing intestinal organoid protocols. CD200 emerged as a pan-EEC surface marker, allowing deep transcriptomic profiling from primary human tissue along the stomach-intestinal tract. We generated loss-of-function mutations in 22 receptors and subjected organoids to ligand-induced secretion experiments. We delineate the role of individual human EEC sensors in the secretion of hormones, including GLP-1. These represent potential pharmacological targets to influence appetite, bowel movement, insulin sensitivity, and mucosal immunity.
DOI: adl1460
Source: https://www.science.org/doi/10.1126/science.adl1460