Single cell transcriptomic profiling of large intestinal enteroendocrine cells in mice - Identification of selective stimuli for insulin-like peptide-5 and glucagon-like peptide-1 co-expressing cells
dc.contributor.author | Billing, Lawrence J. | |
dc.contributor.author | Larraufie, Pierre | |
dc.contributor.author | Lewis, Jo | |
dc.contributor.author | Leiter, Andrew B. | |
dc.contributor.author | Li, Joyce H. | |
dc.contributor.author | Lam, Brian | |
dc.contributor.author | Yeo, Giles Sh. | |
dc.contributor.author | Goldspink, Deborah A. | |
dc.contributor.author | Kay, Richard G. | |
dc.contributor.author | Gribble, Fiona M. | |
dc.contributor.author | Reimann, Frank | |
dc.date | 2022-08-11T08:09:54.000 | |
dc.date.accessioned | 2022-08-23T16:48:29Z | |
dc.date.available | 2022-08-23T16:48:29Z | |
dc.date.issued | 2019-11-01 | |
dc.date.submitted | 2019-12-12 | |
dc.identifier.citation | <p>Mol Metab. 2019 Nov;29:158-169. doi: 10.1016/j.molmet.2019.09.001. Epub 2019 Sep 7. <a href="https://doi.org/10.1016/j.molmet.2019.09.001">Link to article on publisher's site</a></p> | |
dc.identifier.issn | 2212-8778 (Linking) | |
dc.identifier.doi | 10.1016/j.molmet.2019.09.001 | |
dc.identifier.pmid | 31668387 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/41282 | |
dc.description.abstract | OBJECTIVE: Enteroendocrine cells (EECs) of the large intestine, found scattered in the epithelial layer, are known to express different hormones, with at least partial co-expression of different hormones in the same cell. Here we aimed to categorize colonic EECs and to identify possible targets for selective recruitment of hormones. METHODS: Single cell RNA-sequencing of sorted enteroendocrine cells, using NeuroD1-Cre x Rosa26-EYFP mice, was used to cluster EECs from the colon and rectum according to their transcriptome. G-protein coupled receptors differentially expressed across clusters were identified, and, as a proof of principle, agonists of Agtr1a and Avpr1b were tested as candidate EEC secretagogues in vitro and in vivo. RESULTS: EECs from the large intestine separated into 7 clear clusters, 4 expressing higher levels of Tph1 (enzyme required for serotonin (5-HT) synthesis; enterochromaffin cells), 2 enriched for Gcg (encoding glucagon-like peptide-1, GLP-1, L-cells), and the 7th expressing somatostatin (D-cells). Restricted analysis of L-cells identified 4 L-cell sub-clusters, exhibiting differential expression of Gcg, Pyy (Peptide YY), Nts (neurotensin), Insl5 (insulin-like peptide 5), Cck (cholecystokinin), and Sct (secretin). Expression profiles of L- and enterochromaffin cells revealed the clustering to represent gradients along the crypt-surface (cell maturation) and proximal-distal gut axes. Distal colonic/rectal L-cells differentially expressed Agtr1a and the ligand angiotensin II was shown to selectively increase GLP-1 and PYY release in vitro and GLP-1 in vivo. CONCLUSION: EECs in the large intestine exhibit differential expression gradients along the crypt-surface and proximal-distal axes. Distal L-cells can be differentially stimulated by targeting receptors such as Agtr1a. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31668387&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.rights | Copyright 2019 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Enteroendocrine cells | |
dc.subject | Glucagon-like peptide-1 (GLP-1) | |
dc.subject | Insulin-like peptide-5 (Insl5) | |
dc.subject | Serotonin (5-HT) | |
dc.subject | Single cell RNA-sequencing | |
dc.subject | Cell Biology | |
dc.subject | Cellular and Molecular Physiology | |
dc.subject | Digestive System | |
dc.subject | Gastroenterology | |
dc.subject | Molecular Biology | |
dc.title | Single cell transcriptomic profiling of large intestinal enteroendocrine cells in mice - Identification of selective stimuli for insulin-like peptide-5 and glucagon-like peptide-1 co-expressing cells | |
dc.type | Journal Article | |
dc.source.journaltitle | Molecular metabolism | |
dc.source.volume | 29 | |
dc.identifier.legacyfulltext | https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5088&context=oapubs&unstamped=1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/oapubs/4069 | |
dc.identifier.contextkey | 15986389 | |
refterms.dateFOA | 2022-08-23T16:48:29Z | |
html.description.abstract | <p>OBJECTIVE: Enteroendocrine cells (EECs) of the large intestine, found scattered in the epithelial layer, are known to express different hormones, with at least partial co-expression of different hormones in the same cell. Here we aimed to categorize colonic EECs and to identify possible targets for selective recruitment of hormones.</p> <p>METHODS: Single cell RNA-sequencing of sorted enteroendocrine cells, using NeuroD1-Cre x Rosa26-EYFP mice, was used to cluster EECs from the colon and rectum according to their transcriptome. G-protein coupled receptors differentially expressed across clusters were identified, and, as a proof of principle, agonists of Agtr1a and Avpr1b were tested as candidate EEC secretagogues in vitro and in vivo.</p> <p>RESULTS: EECs from the large intestine separated into 7 clear clusters, 4 expressing higher levels of Tph1 (enzyme required for serotonin (5-HT) synthesis; enterochromaffin cells), 2 enriched for Gcg (encoding glucagon-like peptide-1, GLP-1, L-cells), and the 7th expressing somatostatin (D-cells). Restricted analysis of L-cells identified 4 L-cell sub-clusters, exhibiting differential expression of Gcg, Pyy (Peptide YY), Nts (neurotensin), Insl5 (insulin-like peptide 5), Cck (cholecystokinin), and Sct (secretin). Expression profiles of L- and enterochromaffin cells revealed the clustering to represent gradients along the crypt-surface (cell maturation) and proximal-distal gut axes. Distal colonic/rectal L-cells differentially expressed Agtr1a and the ligand angiotensin II was shown to selectively increase GLP-1 and PYY release in vitro and GLP-1 in vivo.</p> <p>CONCLUSION: EECs in the large intestine exhibit differential expression gradients along the crypt-surface and proximal-distal axes. Distal L-cells can be differentially stimulated by targeting receptors such as Agtr1a.</p> | |
dc.identifier.submissionpath | oapubs/4069 | |
dc.contributor.department | Division of Gastroenterology, Department of Medicine | |
dc.source.pages | 158-169 |