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Species: human
Number of cells: 4241
Study size: 142MB

Cell development 

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Beumer, Joep and Puschhof, Jens and Bauza-Martinez, Julia and Martinez-Silgado, Adriana and Elmentaite, Rasa and James, Kylie R and Ross, Alexander and Hendriks, Delilah and Artegiani, Benedetta and Busslinger, Georg A and others

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.

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