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

First Author  McCracken KW Year  2017
Journal  Nature Volume  541
Issue  7636 Pages  182-187
PubMed ID  28052057 Mgi Jnum  J:243618
Mgi Id  MGI:5909197 Doi  10.1038/nature21021
Citation  McCracken KW, et al. (2017) Wnt/beta-catenin promotes gastric fundus specification in mice and humans. Nature 541(7636):182-187
abstractText  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/beta-catenin signalling in mouse embryos led to conversion of fundic to antral epithelium, and that beta-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.
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