B cells exert traction forces on antigen-presenting surfaces during activation.

The human stomach features distinct, regionalized functionalities along the anterior–posterior axis^1,2. Historically, studies on stomach patterning have used animal models to identify the underlying principles^3,4,5,6,7. Recently, human pluripotent stem (hPS)-cell-based gastric organoids for modelling domain-specific development of the fundic and antral epithelium are emerging^8,9,10. 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.

Cyclic mechanical stretching, including uniaxial strain, has been manifested to regulate the cell morphology and functions directly. In recent years, many techniques have been developed to apply cyclic mechanical stretching to cells in vitro. Pneumatically actuated stretching is one of the extensively used methods owing to its advantages of integration, miniaturization, and long-term stretching. However, the intrinsic difficulty in fabrication and adjusting the strain mode also impedes its development and application. In this study, inspired by the topological defects principle, we incorporated a ridge structure into the membrane surface of a traditional pneumatic cavity stretching chip to regulate the strain mode. Our results showed that the surface ridge structure can directly change the equiaxial stretching mode to the standard uniaxial strain, and it is ridge width-independent. The uniaxial strain mode was further proved by the cell orientation behavior under cyclic stretching stimulation. Moreover, it is easy to realize the multimodal strain fields by controlling the width and height of the ridge and to achieve high-throughput testing by creating a cavity array using microfabrication. Together, we propose a smart method to change the surface strain field and introduce a simple, yet effective, high-throughput pneumatically actuated uniaxial stretching platform, which can not only realize the multimodal mechanical stimulation but also achieve multiscale mechanosensing behaviors of single-cell or multi-cell (tissue and/or organoid) mechanobiology applications.