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

Author

Listed:
  • 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
    Cincinnati Children’s Hospital Medical Center)

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.

Suggested Citation

  • Kyle W. McCracken & Eitaro Aihara & Baptiste Martin & Calyn M. Crawford & Taylor Broda & Julie Treguier & Xinghao Zhang & John M. Shannon & Marshall H. Montrose & James M. Wells, 2017. "Wnt/β-catenin promotes gastric fundus specification in mice and humans," Nature, Nature, vol. 541(7636), pages 182-187, January.
    • Handle: RePEc:nat:nature:v:541:y:2017:i:7636:d:10.1038_nature21021
    DOI: 10.1038/nature21021
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