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

First Author  Huebner AJ Year  2023
Journal  Nat Cell Biol Volume  25
Issue  3 Pages  390-403
PubMed ID  36717627 Mgi Jnum  J:372651
Mgi Id  MGI:8249758 Doi  10.1038/s41556-022-01079-4
Citation  Huebner AJ, et al. (2023) Dissection of gastric homeostasis in vivo facilitates permanent capture of isthmus-like stem cells in vitro. Nat Cell Biol 25(3):390-403
abstractText  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.
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