清华大学课题组报道了人类胃模拟早期胃发育的区域模式。相关论文于2025年9月10日发表在《自然》杂志上。

在这里，研究小组报道了人类胃——一种源自hPS细胞的自组织多谱系胃类器官——在体外模拟胃基底-胃窦模式。通过多胚层共同发育，研究组产生的胃具有双极基底-心房模式的上皮腔，与基底区附近的神经群相连，同时被间充质细胞包裹，因此在分子、细胞、结构和解剖上与体内胃发育相似。非内胚层细胞，尤其是神经细胞群，作为一个关键的信号中心，通过WNT介导的串扰来指导胃基底-心房模式。单细胞转录组学分析和基因沉默进一步揭示了NR2F2是胃底-心房模式发育的关键介质。该研究揭示了指导胃模式的原理，为推进胃器官发生和胃类器官发育的知识提供了一个更高保真度的平台。

据悉，人类胃沿前后轴具有明显的区域功能。从历史上看，胃模式的研究以动物模型为主题，以确定潜在的原理。最近，基于人类多能干细胞（hPS）的胃类器官正在出现，用于模拟基底和胃窦上皮特定区域的发育。然而，在早期胃器官发生中再现自组织的基底-心房模式仍然具有挑战性，这对推进胃器官发生的知识提出了相当大的障碍。

附：英文原文

Title: Human gastroids to model regional patterning in early stomach development

Author: Li, Xia, Lin, Feng, Cui, Qiqi, Sun, Shiyu, Li, Shixin, Wang, Yue, Wang, Yiting, Bai, Jianbo, Liu, Shiyi, Guo, Jia, Han, Yizhao, Zhang, Meiru, Chang, Tie, Zheng, Yifan, Liu, Jianlin, Liu, Longqi, Wang, Leyun, Fu, Jianping, Liu, Xin, Bai, Bing, Shao, Yue

Issue&Volume: 2025-09-10

Abstract: The human stomach features distinct, regionalized functionalities along the anterior–posterior axis1,2. Historically, studies on stomach patterning have used animal models to identify the underlying principles3,4,5,6,7. Recently, human pluripotent stem (hPS)-cell-based gastric organoids for modelling domain-specific development of the fundic and antral epithelium are emerging8,9,10. However, recapitulating self-organized fundic–antral patterning in early stomach organogenesis remains challenging, presenting a considerable barrier for advancing knowledge of stomach organogenesis. Here we report human gastroids—a self-organized multilineage gastric organoid derived from hPS cells—to model gastric fundic–antral patterning in vitro. Through multi-germ-layer co-development, we generate gastroids that feature an epithelial chamber with bipolar fundic–antral patterning, annexed with neural populations near the fundic domain while enveloped by mesenchymal cells, therefore showing molecular, cellular, structural and anatomical similarity to stomach development in vivo. Non-endodermal cells, especially neural populations, function as a critical signalling centre to instruct fundic–antral patterning in gastroids through WNT-mediated crosstalk. Single-cell transcriptomic profiling and genetic silencing further reveal NR2F2 as a key mediator of fundic–antral patterning in gastroid development. This study reveals a principle for instructing gastric patterning and provides a higher-fidelity platform for advancing knowledge of stomach organogenesis and gastric organoid development.

DOI: 10.1038/s41586-025-09508-8

Source: https://www.nature.com/articles/s41586-025-09508-8