Deriving functional human enteroendocrine cells from pluripotent stem cells.

Development
Katie L SinagogaJames M Wells

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.

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Citations

Sep 11, 2019·The Journal of Nutrition·Heather A McCauley
Jun 22, 2019·Cell and Tissue Research·José E García-ArrarásSunny Qi-Huang
Jul 14, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Akaljot SinghMichael A Helmrath
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Jan 21, 2020·Frontiers in Medicine·Abdelkader Daoud, Jorge O Múnera
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Jan 5, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Ichiro Sakata, Shota Takemi
Oct 28, 2021·The EMBO Journal·Andrew E RosselotChristian I Hong

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