High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells
High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells
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DOI：
10.1016/j.cell.2020.04.036
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发表时间：
2020-06-11
期刊：
影响因子：
64.5
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Beumer, Joep;Puschhof, Jens;Clevers, Hans
肠内分泌细胞（EECs）感知肠道内容物并释放激素来调节胃肠道活动、全身代谢和食物摄入。关于人类EEC亚型的分子组成和个体激素的调节分泌知之甚少。在这里，我们描述了一个基于类器官的平台，用于人类内皮细胞的功能研究。EEC的形成在体外由NEUROG 3的瞬时表达诱导。设计了一组肠道类器官，其中主要激素被荧光标记。一个单细胞的mRNA图谱产生的不同EEC亚型，并通过质谱法记录其分泌的产品。我们注意到小鼠内皮细胞的关键差异，包括激素，感觉受体和转录因子。值得注意的是，鉴定了几种类胡萝卜素分子。EEC间通讯的例子是促分泌素诱导的GLP-1分泌。事实上，个别EEC亚型携带各种EEC激素的受体。本研究为进一步研究人体脑电的发育和功能提供了丰富的资料。
Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.