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dc.contributor.authorBilling, Lawrence J.
dc.contributor.authorLarraufie, Pierre
dc.contributor.authorLewis, Jo
dc.contributor.authorLeiter, Andrew B.
dc.contributor.authorLi, Joyce H.
dc.contributor.authorLam, Brian
dc.contributor.authorYeo, Giles Sh.
dc.contributor.authorGoldspink, Deborah A.
dc.contributor.authorKay, Richard G.
dc.contributor.authorGribble, Fiona M.
dc.contributor.authorReimann, Frank
dc.date2022-08-11T08:09:54.000
dc.date.accessioned2022-08-23T16:48:29Z
dc.date.available2022-08-23T16:48:29Z
dc.date.issued2019-11-01
dc.date.submitted2019-12-12
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.issn2212-8778 (Linking)
dc.identifier.doi10.1016/j.molmet.2019.09.001
dc.identifier.pmid31668387
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41282
dc.description.abstractOBJECTIVE: 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.isoen_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.rightsCopyright 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.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectEnteroendocrine cells
dc.subjectGlucagon-like peptide-1 (GLP-1)
dc.subjectInsulin-like peptide-5 (Insl5)
dc.subjectSerotonin (5-HT)
dc.subjectSingle cell RNA-sequencing
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectDigestive System
dc.subjectGastroenterology
dc.subjectMolecular Biology
dc.titleSingle 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.typeJournal Article
dc.source.journaltitleMolecular metabolism
dc.source.volume29
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5088&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4069
dc.identifier.contextkey15986389
refterms.dateFOA2022-08-23T16:48:29Z
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.submissionpathoapubs/4069
dc.contributor.departmentDivision of Gastroenterology, Department of Medicine
dc.source.pages158-169


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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/).
Except where otherwise noted, this item's license is described as 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/).