Mesenchymal-epithelial interaction guides development of stomach and intestine in mouse embryos

After gut tube patterning in early embryos, the cellular and molecular changes of developing stomach and intestine remain largely unknown. Here, combining single-cell RNA-sequencing and spatial RNA-sequencing, we constructed a spatiotemporal transcriptomic landscape of the mouse stomach and intestine during embryonic day E9.5-E15.5. We observed regionalization and heterogeneity of both the epithelium and mesenchyme in the gastrointestinal (GI) tract at E9.5 and dynamic cell evolution afterwards. The spatiotemporal distributions of cell clusters and the epithelium-mesenchyme interactions indicate a coordinated development of the epithelium and mesenchyme. The cell evolution and signaling events regulate the stomach regionalization and intestine segmentation. Using the gut tube-derived organoids, we found that the cell fate of the foregut and hindgut could be switched by the regional niche factors. Together, this work demonstrates the important function of the epithelium-mesenchyme interactions in early GI tract development, laying a foundation for further dissection of the mechanisms governing this process. Overall design: Constructing single cell atlas of mouse embyro stomach and intestine during E9.5-E15.5.