High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells.
CRISPR-mediated knockin
enteroendocrine cell
fluorescent tagging
hormone
human
intestine
organoids
proteomics
secretomics
single-cell atlas
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
11 06 2020
11 06 2020
Historique:
received:
29
11
2019
revised:
10
03
2020
accepted:
21
04
2020
pubmed:
15
5
2020
medline:
5
1
2021
entrez:
15
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32407674
pii: S0092-8674(20)30501-8
doi: 10.1016/j.cell.2020.04.036
pii:
doi:
Substances chimiques
Gastrointestinal Hormones
0
RNA, Messenger
0
Transcription Factors
0
Glucagon-Like Peptide 1
89750-14-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1291-1306.e19Subventions
Organisme : Cancer Research UK
ID : C10674/A27140
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests H.C. is inventor on several patents related to organoid technology; his full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. is founder of OrganoidZ, which employs organoids for drug development. J.B., J.P., and H.C. are inventors on patents related to this work.