Format

Send to

Choose Destination
Development. 2018 Oct 1;145(19). pii: dev165795. doi: 10.1242/dev.165795.

Deriving functional human enteroendocrine cells from pluripotent stem cells.

Author information

1
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA.
2
Endocrine/Cardiovascular Division, Eli Lilly and Company, Indianapolis, IN 46285, USA.
3
Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA.
4
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA.
5
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA james.wells@cchmc.org.
6
Division of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA.

Abstract

Enteroendocrine cells (EECs) are a minor cell population in the intestine yet they play a major role in digestion, satiety and nutrient homeostasis. Recently developed human intestinal organoid models include EECs, but their rarity makes it difficult to study their formation and function. Here, we used the EEC-inducing property of the transcription factor NEUROG3 in human pluripotent stem cell-derived human intestinal organoids and colonic organoids to promote EEC development in vitro An 8-h pulse of NEUROG3 expression induced expression of known target transcription factors and after 7 days organoids contained up to 25% EECs in the epithelium. EECs expressed a broad array of human hormones at the mRNA and/or protein level, including motilin, somatostatin, neurotensin, secretin, substance P, serotonin, vasoactive intestinal peptide, oxyntomodulin, GLP-1 and INSL5. EECs secreted several hormones including gastric inhibitory polypeptide (GIP), ghrelin, GLP-1 and oxyntomodulin. Injection of glucose into the lumen of organoids caused an increase in both GIP secretion and K-cell number. Lastly, we observed formation of all known small intestinal EEC subtypes following transplantation and growth of human intestinal organoids in mice.

KEYWORDS:

Hormones; Incretin; Neurogenin 3; Organoids; Satiety; Stem cell

PMID:
30143540
PMCID:
PMC6198470
[Available on 2019-10-01]
DOI:
10.1242/dev.165795
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center