%0 Journal Article %T 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 %+ Wellcome Trust-MRC Institute of Metabolic Science %A Billing, Lawrence, J %A Larraufie, Pierre %A Lewis, Jo %A Leiter, Andrew %A Li, Joyce %A Lam, Brian %A Yeo, Giles, Sh %A Goldspink, Deborah, A %A Kay, Richard, G %A Gribble, Fiona, M %A Reimann, Frank %< avec comité de lecture %@ 2212-8778 %J Molecular metabolism %I Elsevier %V 29 %P 158-169 %8 2019-11 %D 2019 %R 10.1016/j.molmet.2019.09.001 %K Single cell RNA-sequencing %K Enteroendocrine cells %K Glucagon-like peptide-1 (GLP-1) %K Insulin-like peptide-5 (Insl5) %K Serotonin (5-HT) %Z Life Sciences [q-bio]/Cellular Biology %Z Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolismJournal articles %X 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 Land 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. %G English %2 https://agroparistech.hal.science/hal-03450647/document %2 https://agroparistech.hal.science/hal-03450647/file/1-s2.0-S2212877819307628-main.pdf %L hal-03450647 %U https://agroparistech.hal.science/hal-03450647 %~ AGROPARISTECH