Enteroendocrine cell lineages that differentially control feeding and gut motility
- Howard Hughes Medical Institute, Harvard Medical School, United States
- University of Cambridge, United Kingdom
Abstract
Enteroendocrine cells are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium. The functions of enteroendocrine cells have classically been inferred by the gut hormones they release. However, individual enteroendocrine cells typically produce multiple, sometimes apparently opposing, gut hormones in combination, and some gut hormones are also produced elsewhere in the body. Here, we developed approaches involving intersectional genetics to enable selective access to enteroendocrine cells in vivo in mice. We targeted FlpO expression to the endogenous Villin1 locus (in Vil1-p2a-FlpO knock-in mice) to restrict reporter expression to intestinal epithelium. Combined use of Cre and Flp alleles effectively targeted major transcriptome-defined enteroendocrine cell lineages that produce serotonin, glucagon-like peptide 1, cholecystokinin, somatostatin, or glucose-dependent insulinotropic polypeptide. Chemogenetic activation of different enteroendocrine cell types variably impacted feeding behavior and gut motility. Defining the physiological roles of different enteroendocrine cell types provides an essential framework for understanding sensory biology of the intestine.
Data availability
The source data excel file contains raw numerical data used for all bar graphs and statistical analyses. Single-cell transcriptome data are available at NCBI Gene Expression Omnibus with accession GSE224223
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nteroendocrine cell lineages that differentially control feeding and gut motilityNCBI Gene Expression Omnibus, GSE224223.
Article and author information
Author details
Stephen D Liberles
Funding
Food Allergy Science Initiative (n/A)
- Stephen D Liberles
National Institutes of Health (DP1AT009497)
- Stephen D Liberles
National Institutes of Health (R01DK103703)
- Stephen D Liberles
Howard Hughes Medical Institute (n/a)
- Stephen D Liberles
Japan Society for the Promotion of Science (n/a)
- Marito Hayashi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal husbandry and procedures were performed in compliance with institutional animal care and use committee guidelines. All animal husbandry and procedures followed the ethical guidelines outlined in the NIH Guide for the Care and Use of Laboratory Animals (https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-of-laboratory-animals.pdf), and all protocols were approved by the institutional animal care and use committee (IACUC) at Harvard Medical School.
Copyright
© 2023, Hayashi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Enteroendocrine cell lineages that differentially control feeding and gut motility
eLife 12:e78512.
https://doi.org/10.7554/eLife.78512
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