解剖胃内稳态有助于在体内永久捕获类似峡部干细胞。
Dissection of gastric homeostasis in vivo facilitates permanent capture of isthmus-like stem cells in vitro.
发表日期：2023 Jan 30
作者：
Aaron J Huebner, Rebecca A Gorelov, Ruslan Deviatiiarov, Samuel Demharter, Tobias Kull, Ryan M Walsh, Marty S Taylor, Simon Steiger, John T Mullen, Peter V Kharchenko, Konrad Hochedlinger
来源：
NATURE CELL BIOLOGY
摘要：
腺胃由称为胃体和胃窦的两个再生隔间组成，我们对于维持这些组织的转录网络的理解还不完整。在这里，我们展示了在胃体和胃窦中具有相同功能角色的细胞类型具有相似的转录状态，包括难以确定的峡部干细胞。为了进一步研究峡部，我们开发了一个单层二维（2D）培养系统，由能够分化成几种胃细胞类型的Wnt响应的峡部样细胞不断维持。重要的是，2D培养可以转化为传统的三维器官样体，模拟体内胃上皮细胞的可塑性。最后，我们利用2D培养系统展示了Sox2在生成肠腺染色细胞方面既必要又充分。综上所述，我们的数据提供了有关胃内环境稳态的重要见解，建立了一个可处理的培养系统以捕捉峡部细胞，并揭示了Sox2在肠腺染色细胞中的作用。 © 2023年。作者（们）独家授权Springer Nature Limited。
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.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.