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<p>Patient-derived human organoids have the capacity to self-organize into more complex structures. However, to what extent gastric organoids can recapitulate differentiated cell types and mucosal functions remains unexplored. Here we report on how region-specific gastric organoids can self-assemble into complex multi-regional assembloids. These assembloids show increased complexity and cross-communication between different gastric regions, allowing for the emergence of the elusive parietal cell type that is responsible for the production of gastric acid and shows a functional response to drugs targeting the H<sup>+</sup>/K<sup>+</sup> ATPase pump. We generate assembloids from paediatric patients with a genetic condition found to be associated with unusual antral foveolar hyperplasia and hyperplastic polyposis. Our multi-regional assembloid efficiently recapitulates hyperplastic-like antral regions, with decreased mucin secretion and glycosylated H<sup>+</sup>/K<sup>+</sup> ATPase subunit beta, which results in impaired gastric acid secretion. Multi-regional gastric assembloids, generated using paediatric-stem-cell-derived organoids, successfully recapitulate the structural and functional characteristics of the human stomach, offering a promising tool for studying gastric epithelial interactions and disease mechanisms that were previously challenging to investigate in primary models.</p>

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Human gastric multi-regional assembloids for functional parietal maturation and patient-specific modelling of antral foveolar hyperplasia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Brendan C. Jones,
  • Giada Benedetti,
  • Giuseppe Calà,
  • Ramin Amiri,
  • Lucinda Tullie,
  • Roberto Lutman,
  • Jahangir Sufi,
  • Lucy Holland,
  • Daniyal J. Jafree,
  • Monika Balys,
  • Glenn Anderson,
  • Ian C. Simcock,
  • Owen J. Arthurs,
  • Simon Eaton,
  • Nicola Elvassore,
  • Vivian SW Li,
  • Christopher J. Tape,
  • Kelsey DJ Jones,
  • Camilla Luni,
  • Giovanni Giuseppe Giobbe,
  • Paolo De Coppi

摘要

Patient-derived human organoids have the capacity to self-organize into more complex structures. However, to what extent gastric organoids can recapitulate differentiated cell types and mucosal functions remains unexplored. Here we report on how region-specific gastric organoids can self-assemble into complex multi-regional assembloids. These assembloids show increased complexity and cross-communication between different gastric regions, allowing for the emergence of the elusive parietal cell type that is responsible for the production of gastric acid and shows a functional response to drugs targeting the H+/K+ ATPase pump. We generate assembloids from paediatric patients with a genetic condition found to be associated with unusual antral foveolar hyperplasia and hyperplastic polyposis. Our multi-regional assembloid efficiently recapitulates hyperplastic-like antral regions, with decreased mucin secretion and glycosylated H+/K+ ATPase subunit beta, which results in impaired gastric acid secretion. Multi-regional gastric assembloids, generated using paediatric-stem-cell-derived organoids, successfully recapitulate the structural and functional characteristics of the human stomach, offering a promising tool for studying gastric epithelial interactions and disease mechanisms that were previously challenging to investigate in primary models.