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Nature. 2017 Jan 12;541(7636):182-187. doi: 10.1038/nature21021. Epub 2017 Jan 4.

Wnt/β-catenin promotes gastric fundus specification in mice and humans.

Author information

1
Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
2
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
3
Division of Pulmonary Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
4
Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

Abstract

Despite the global prevalence of gastric disease, there are few adequate models in which to study the fundus epithelium of the human stomach. We differentiated human pluripotent stem cells (hPSCs) into gastric organoids containing fundic epithelium by first identifying and then recapitulating key events in embryonic fundus development. We found that disruption of Wnt/β-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that β-catenin activation in hPSC-derived foregut progenitors promoted the development of human fundic-type gastric organoids (hFGOs). We then used hFGOs to identify temporally distinct roles for multiple signalling pathways in epithelial morphogenesis and differentiation of fundic cell types, including chief cells and functional parietal cells. hFGOs are a powerful model for studying the development of the human fundus and the molecular bases of human gastric physiology and pathophysiology, and also represent a new platform for drug discovery.

PMID:
28052057
PMCID:
PMC5526592
DOI:
10.1038/nature21021
[Indexed for MEDLINE]
Free PMC Article

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