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

Kyle W. McCracken, Eitaro Aihara, Baptiste Martin, Calyn M. Crawford, Taylor Broda, Julie Treguier, Xinghao Zhang, John M. Shannon, Marshall H. Montrose and James M. Wells ()
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Kyle W. McCracken: Cincinnati Children’s Hospital Medical Center
Eitaro Aihara: University of Cincinnati College of Medicine
Baptiste Martin: Cincinnati Children’s Hospital Medical Center
Calyn M. Crawford: Cincinnati Children’s Hospital Medical Center
Taylor Broda: Cincinnati Children’s Hospital Medical Center
Julie Treguier: Cincinnati Children’s Hospital Medical Center
Xinghao Zhang: Cincinnati Children’s Hospital Medical Center
John M. Shannon: Cincinnati Children’s Hospital Medical Center
Marshall H. Montrose: University of Cincinnati College of Medicine
James M. Wells: Cincinnati Children’s Hospital Medical Center

Nature, 2017, vol. 541, issue 7636, 182-187

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature21021

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