Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract.

Autor: Smith CA; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., O'Flaherty EAA; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Guccio N; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Punnoose A; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Darwish T; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Lewis JE; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Foreman RE; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Li J; Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America., Kay RG; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Adriaenssens AE; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Reimann F; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom., Gribble FM; Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, United Kingdom.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Oct 08; Vol. 19 (10), pp. e0308942. Date of Electronic Publication: 2024 Oct 08 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0308942
Abstrakt: Background: Enteroendocrine cells (EECs) produce over 20 gut hormones which contribute to intestinal physiology, nutrient metabolism and the regulation of food intake. The objective of this study was to generate a comprehensive transcriptomic map of mouse EECs from the stomach to the rectum.
Methods: EECs were purified by flow-cytometry from the stomach, upper small intestine, lower small intestine, caecum and large intestine of NeuroD1-Cre mice, and analysed by single cell RNA sequencing. Regional datasets were analysed bioinformatically and combined into a large cluster map. Findings were validated by L-cell calcium imaging and measurements of CCK secretion in vitro.
Results: 20,006 EECs across the full gastrointestinal tract could be subdivided based on their full transcriptome into 10 major clusters, each exhibiting a different pattern of gut hormone expression. EECs from the stomach were largely distinct from those found more distally, even when expressing the same hormone. Cell clustering was also observed when performed only using genes related to GPCR cell signalling, revealing GPCRs predominating in different EEC populations. Mc4r was expressed in 55% of Cck-expressing cells in the upper small intestine, where MC4R agonism was found to stimulate CCK release in primary cultures. Many individual EECs expressed more than one hormone as well as machinery for activation by multiple nutrients, which was supported by the finding that the majority of L-cells exhibited calcium responses to multiple stimuli.
Conclusions: This comprehensive transcriptomic map of mouse EECs reveals patterns of GPCR and hormone co-expression that should be helpful in predicting the effects of nutritional and pharmacological stimuli on EECs from different regions of the gut. The finding that MC4R agonism stimulates CCK secretion adds to our understanding of the melanocortin system.
Competing Interests: “FMG and FR have received funding for other projects from AstraZeneca and Eli Lilly. LGC provided partial salary support for REF, but was not otherwise involved with this study. Since completing the work, REF moved to work for AstraZeneca which has had no involvement with the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”
(Copyright: © 2024 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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