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Human gastroids to model regional patterning in early stomach development.

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Summary

Researchers developed human gastroids, a novel gastric organoid model, to study stomach development. These organoids mimic in vivo stomach patterning, revealing neural cells and NR2F2 as key factors in fundic-antral patterning.

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Gastroenterology

Background:

  • The human stomach exhibits regional functional differences along its anterior-posterior axis.
  • Animal models have historically informed stomach patterning studies.
  • Human pluripotent stem (hPS)-cell-based gastric organoids are emerging but struggle to model early fundic-antral patterning.

Purpose of the Study:

  • To develop a self-organized human gastric organoid model (gastroids) for studying fundic-antral patterning in vitro.
  • To investigate the cellular and molecular mechanisms underlying gastric patterning during early organogenesis.

Main Methods:

  • Generation of self-organized multilineage gastric organoids (gastroids) from hPS cells.
  • Co-development involving multiple germ layers to mimic in vivo development.
  • Single-cell transcriptomic profiling and genetic silencing to identify key signaling pathways and genes.

Main Results:

  • Gastroids exhibit bipolar fundic-antral epithelial patterning, neural populations, and mesenchymal cells, mirroring in vivo stomach development.
  • Non-endodermal cells, particularly neural populations, act as signaling centers instructing patterning via WNT-mediated crosstalk.
  • NR2F2 was identified as a crucial mediator of fundic-antral patterning in gastroid development.

Conclusions:

  • Human gastroids provide a high-fidelity in vitro model for studying gastric fundic-antral patterning.
  • This study elucidates a principle for instructing gastric patterning, involving neural signaling and the NR2F2 gene.
  • The findings advance the understanding of stomach organogenesis and the development of gastric organoids.