Dissection of gastric homeostasis in vivo facilitates permanent capture of isthmus-like stem cells in vitro

Huebner et al. develop a 2D culture system to study gastric isthmus stem cells and identify a role for Sox2 in specifying enterochromaffin cells in the stomach. The glandular stomach is composed of two regenerative compartments termed corpus and antrum, and our understanding of the transcriptional networks that maintain these tissues is incomplete. Here we show that cell types with equivalent functional roles in the corpus and antrum share similar transcriptional states including the poorly characterized stem cells of the isthmus region. To further study the isthmus, we developed a monolayer two-dimensional (2D) culture system that is continually maintained by Wnt-responsive isthmus-like cells capable of differentiating into several gastric cell types. Importantly, 2D cultures can be converted into conventional three-dimensional organoids, modelling the plasticity of gastric epithelial cells in vivo. Finally, we utilized the 2D culture system to show that Sox2 is both necessary and sufficient to generate enterochromaffin cells. Together, our data provide important insights into gastric homeostasis, establish a tractable culture system to capture isthmus cells and uncover a role for Sox2 in enterochromaffin cells.

Automated summary

Huebner et al. developed a 2D culture system to study gastric isthmus stem cells and found that Sox2 plays a role in specifying enterochromaffin cells in the stomach. They showed that cell types in the corpus and antrum regions share similar transcriptional states, including the poorly characterized isthmus stem cells. The 2D culture system can be converted into 3D organoids and was used to demonstrate the importance of Sox2 in generating enterochromaffin cells.