荷兰皇家艺术学院（KNAW）和UMC乌得勒支（荷兰）Hans Clevers研究组在研究中取得进展。他们绘制了人肠内分泌细胞（EEC）的高分辨率mRNA和分泌组图谱。2020年5月13日国际知名学术期刊《细胞》发表了这一成果。
他们描述了一个基于类器官的平台，用于人类EEC的功能研究。通过瞬时表达NEUROG3在体外诱导EEC的形成。他们设计了一套肠道类器官，其中的主要激素被荧光标记。为不同的EEC亚型生成了单细胞mRNA图谱，并通过质谱法记录了它们的分泌产物。他们注意到与鼠类EEC的主要区别，包括激素、感觉受体和转录因子。值得注意的是，鉴定了几种激素样分子。EEC间的交流以促胰液素诱导的GLP-1分泌为例。实际上，单个EEC亚型携带着各种EEC激素的受体。这项研究为研究人类EEC的发育和功能提供了丰富的资源。
研究人员表示，EEC感知肠内物质并释放激素以调节肠胃活动、全身代谢和食物摄入。关于人类EEC亚型的分子组成以及个别激素的调节分泌知之甚少。
附：英文原文
Title: High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells
Author: Joep Beumer, Jens Puschhof, Julia Bauzá-Martinez, Adriana Martínez-Silgado, Rasa Elmentaite, Kylie R. James, Alexander Ross, Delilah Hendriks, Benedetta Artegiani, Georg A. Busslinger, Bas Ponsioen, Amanda Andersson-Rolf, Aurelia Saftien, Charelle Boot, Kai Kretzschmar, Maarten H. Geurts, Yotam E. Bar-Ephraim, Cayetano Pleguezuelos-Manzano, Yorick Post, Harry Begthel, Franka van der Linden, Carmen Lopez-Iglesias, Willine J. van de Wetering, Reinier van der Linden, Peter J. Peters, Albert J.R. Heck, Joachim Goedhart, Hugo Snippert, Matthias Zilbauer, Sarah A. Teichmann, Wei Wu, Hans Clevers
Issue&Volume: 2020-05-13
Abstract: Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulategastrointestinal activity, systemic metabolism, and food intake. Little is known aboutthe molecular make-up of human EEC subtypes and the regulated secretion of individualhormones. Here, we describe an organoid-based platform for functional studies of humanEECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescentlytagged. A single-cell mRNA atlas was generated for the different EEC subtypes, andtheir secreted products were recorded by mass-spectrometry. We note key differencesto murine EECs, including hormones, sensory receptors, and transcription factors.Notably, several hormone-like molecules were identified. Inter-EEC communication isexemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carryreceptors for various EEC hormones. This study provides a rich resource to study humanEEC development and function.
DOI: 10.1016/j.cell.2020.04.036
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30501-8