Proteomics

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High Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells


ABSTRACT: Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity and 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 with murine EECs, including in hormones, sensory receptors and transcription factors. Notably, several novel 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Julia Bauzá Martinez  

LAB HEAD: Wei Wu

PROVIDER: PXD017468 | Pride | 2020-05-15

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
CHGAneg_Proteome_Rep1.msf Msf
CHGAneg_Proteome_Rep1.raw Raw
CHGAneg_Proteome_Rep2.msf Msf
CHGAneg_Proteome_Rep2.raw Raw
CHGAneg_Proteome_Rep3.msf Msf
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Publications

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells.

Beumer Joep J   Puschhof Jens J   Bauzá-Martinez Julia J   Martínez-Silgado Adriana A   Elmentaite Rasa R   James Kylie R KR   Ross Alexander A   Hendriks Delilah D   Artegiani Benedetta B   Busslinger Georg A GA   Ponsioen Bas B   Andersson-Rolf Amanda A   Saftien Aurelia A   Boot Charelle C   Kretzschmar Kai K   Geurts Maarten H MH   Bar-Ephraim Yotam E YE   Pleguezuelos-Manzano Cayetano C   Post Yorick Y   Begthel Harry H   van der Linden Franka F   Lopez-Iglesias Carmen C   van de Wetering Willine J WJ   van der Linden Reinier R   Peters Peter J PJ   Heck Albert J R AJR   Goedhart Joachim J   Snippert Hugo H   Zilbauer Matthias M   Teichmann Sarah A SA   Wu Wei W   Clevers Hans H  

Cell 20200513 6


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 fluores  ...[more]

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