Evidence map›Paper›PMID 31668387›Full record

ArticleMolecular metabolism2019

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.

Lawrence J Billing, Pierre Larraufie, Jo Lewis, Andrew Leiter, Joyce Li, Brian Lam, Giles Sh Yeo, Deborah A Goldspink, Richard G Kay, Fiona M Gribble and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
12.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 112 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Mechanisms and clinical implications of gut-brain interactions.The Journal of clinical investigation · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Incretin hormones and obesity.The Journal of physiology · 2025
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Unique properties of proximal and distal colon reflect distinct motor functions.American journal of physiology. Gastrointestinal and liver physiology · 2025
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Lawrence J BillingUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Pierre LarraufieUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Jo LewisUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Andrew LeiterDivision of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States.
Joyce LiDivision of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States.
Brian LamUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Giles Sh YeoUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Deborah A GoldspinkUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Richard G KayUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
Fiona M GribbleUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom. Electronic address: fmg23@cam.ac.uk.
Frank ReimannUniversity of Cambridge, Wellcome Trust/MRC Institute of Metabolic Science (IMS) & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom. Electronic address: fr222@cam.ac.uk.
Addenbrooke's Hospital · GBUniversity of Massachusetts Chan Medical School · USWellcome/MRC Institute of Metabolic Science · GBWellcome Trust · GB

Funding

Medical Research Council MC_UU_00014/1Medical Research Council MC_UU_00014/3Medical Research Council MC_UU_00014/5Medical Research Council MC_UU_12012/1Medical Research Council MC_UU_12012/3Medical Research Council MC_UU_12012/5Medical Research Council MR/M008975/1Medical Research Council MR/M009041/1Medical Research Council MR/M024873/1Wellcome TrustWellcome Trust 106262/Z/14/ZWellcome Trust 106263/Z/14/Z
6 · The paper itself

Abstract

objectiveEnteroendocrine 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.

methodsSingle 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.

resultsEECs 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.

conclusionEECs 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.

Indexed as

TranscriptomeAnimalsEnteroendocrine CellsFemaleGlucagon-Like Peptide 1InsulinIntestine, LargeMaleMiceMice, Inbred C57BLMice, TransgenicPeptide YYProteinsReceptor, Angiotensin, Type 1Single-Cell AnalysisTryptophan HydroxylaseAgtr1a protein, mouseGlucagon-Like Peptide 1InsulinLeydig insulin-like proteinPeptide YYProteinsReceptor, Angiotensin, Type 1Tph1 protein, mouseTryptophan HydroxylaseEnteroendocrine cellsGlucagon-like peptide-1 (GLP-1)Insulin-like peptide-5 (Insl5)Serotonin (5-HT)Single cell RNA-sequencing

Identifiers

PMID31668387
PMCPMC6812004
OpenAlexW2972141741

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.