Comparative analysis of enteroendocrine cells and their hormones between mouse intestinal organoids and native tissues

Biosci Biotechnol Biochem. 2020 May;84(5):936-942. doi: 10.1080/09168451.2020.1713043. Epub 2020 Jan 9.

Abstract

Endocrine cells in the gastrointestinal tract secrete multiple hormones to maintain homeostasis in the body. In the present study, we generated intestinal organoids from the duodenum, jejunum, and ileum of Neurogenin 3 (Ngn3)-EGFP mice and examined how enteroendocrine cells (EECs) within organoid cultures resemble native epithelial cells in the gut. Transcriptome analysis of EGFP-positive cells from Ngn3-EGFP organoids showed gene expression pattern comparable to EECs in vivo. We also compared mRNAs of five major hormones, namely, ghrelin (Ghrl), cholecystokinin (Cck), Gip, secretin (Sct), and glucagon (Gcg) in organoids and small intestine along the longitudinal axis and found that expression patterns of these hormones in organoids were similar to those in native tissues. These findings suggest that an intestinal organoid culture system can be utilized as a suitable model to study enteroendocrine cell functions in vitro.

Keywords: Ngn3; Organoid; hormone; intestine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cells, Cultured
  • Cholecystokinin / genetics
  • Cholecystokinin / metabolism
  • Duodenum / cytology*
  • Enteroendocrine Cells / metabolism*
  • Gastric Inhibitory Polypeptide / genetics
  • Gastric Inhibitory Polypeptide / metabolism
  • Ghrelin / genetics
  • Ghrelin / metabolism
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism
  • Green Fluorescent Proteins / metabolism
  • Ileum / cytology*
  • Jejunum / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Organoids / cytology*
  • RNA, Messenger / genetics
  • Secretin / genetics
  • Secretin / metabolism
  • Signal Transduction
  • Transcriptome

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Ghrelin
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • RNA, Messenger
  • enhanced green fluorescent protein
  • Secretin
  • Green Fluorescent Proteins
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Cholecystokinin