Human gastroids to model regional patterning in early stomach development
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View abstract on PubMed
Summary
This summary is machine-generated.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.
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.
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