Abstract
Enteroendocrine cells (EECs) produce hormones that regulate food absorption, insulin secretion and appetite. Both EECs and their peptide products are foci of drug discovery programmes for diabetes and obesity. We compared the human and mouse EEC transcriptome and peptidome to validate mouse as a model of the human enteroendocrine axis. We present the first RNA sequencing analysis of human EECs, and demonstrate strong correlation with mouse, although with outliers including some low abundance G-protein coupled receptors. Liquid chromatography mass spectrometry (LC-MS) identified peptide hormone gradients along the human and mouse gut that should enhance progress in gut physiology and therapeutics.
Footnotes
↵ǂ joint first authors
Wellcome Trust – MRC Institute of Metabolic Science, Box 289, Addenbrooke’s Hospital, Cambridge, CB2 0QQ
Grant support:
Metabolic Research Laboratories support was provided by the following core facilities: Disease Model Core, Genomics and Transcriptomics Core, Histology Core, Imaging Core and NIHR BRC Core Biochemical Assay Laboratory (supported by the MRC [MRC_MC_UU_12012/5] and Wellcome Trust [100574/Z/12/Z]). RNA-sequencing was undertaken at the CRUK Cambridge Institute Genomics Core.
GR received an Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69], an EFSD project grant and a Royal College of Surgeons Research Fellowship. SG is supported by a grant from the BBSRC. Research in the laboratory of Fiona Gribble and Frank Reimann is supported by the MRC [MRC_MC_UU_12012/3], Wellcome Trust [106262/Z/14/Z, 106263/Z/14/Z] and research grants from Medimmune. The MS instrument was funded by the MRC “Enhancing UK clinical research” grant (MR/M009041/1). PR was supported by a postdoctoral grant from Agence Nationale de la Recherche (Laboratoire d’Excellence Revive, Investissement d’Avenir; ANR-10-LABX-73). The RS lab is supported by ANR-10-LABX-73 and the Bettencourt-Schueller foundation. This work was partially supported by the following NIH grants to AL: R01 DK100223-02, R01 DK110614-01.
Conflicts of interest
FMG is a paid consultant for, and PR has (subsequent to his work on this project) taken up full time employment with Kallyope, New York. The Gribble-Reimann lab hosts projects which receive funding from Medimmune (FMG / FR). There are no other conflicts of interest to declare.
Data availability statement
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD009788 (10.6019/PXD009788) and PXD009796 (10.6019/PXD009796)(1). RNA-seq data has been deposited in the NCBI GEO repository (human – GSE114853, mouse-GSE114913).