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.

腺胃由两个再生隔室组成，称为胃体和胃窦，我们对维持这些组织的转录网络的理解是不完整的。在这里，我们表明在语料库和胃窦中具有相同功能作用的细胞类型具有相似的转录状态，包括峡部区域特征较差的干细胞。为了进一步研究地峡，我们开发了一种单层二维 (2D) 培养系统，该系统由能够分化为多种胃细胞类型的 Wnt 反应性地峡样细胞持续维持。重要的是，二维培养物可以转化为传统的三维类器官，模拟体内胃上皮细胞的可塑性。最后，我们利用二维培养系统表明Sox2是产生肠嗜铬细胞的必要条件和充分条件。总之，我们的数据提供了对胃稳态的重要见解，建立了一个易于处理的培养系统来捕获峡部细胞，并揭示了 Sox2 在肠嗜铬细胞中的作用。