Mesenchymal-epithelial interaction regulates gastrointestinal tract development in mouse embryos

• Published in: Cell reports (Cambridge) Vol. 40; no. 2; p. 111053
• Main Authors: Zhao, Lianzheng, Song, Wanlu, Chen, Ye-Guang
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 12.07.2022
• Subjects: development; intestine; mesenchymal-epithelial interaction; single-cell RNA-seq; spatial RNA-seq; stomach; mesenchymal-epithelial interaction; development; intestine; single-cell RNA-seq; stomach; CP: Developmental biology; spatial RNA-seq
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111053

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 construct a spatiotemporal transcriptomic landscape of the mouse stomach and intestine during embryonic days E9.5–E15.5. Several subpopulations are identified, including Lox+ stomach mesenchyme, Aldh1a3+ small-intestinal mesenchyme, and Adamdec1+ large-intestinal mesenchyme. The regionalization and heterogeneity of both the epithelium and the mesenchyme can be traced back to E9.5. The spatiotemporal distributions of cell clusters and the mesenchymal-epithelial interaction analysis indicate that a coordinated development of the epithelium and mesenchyme contribute to the stomach regionalization, intestine segmentation, and villus formation. Using the gut tube-derived organoids, we find that the cell fate of the foregut and hindgut can be switched by the regional niche factors, including fibroblast growth factors (FGFs) and retinoic acid (RA). This work lays a foundation for further dissection of the mechanisms governing this process. [Display omitted] •RNA-seq profiling reveals a dynamic cell atlas during early GI tract development•Epithelial and mesenchymal regionalization can be detected at E9.5•Mesenchymal-epithelial interactions regulate developmental events of the GI tract•Gut tube cells possess plasticity and cell fate can be switched by regional factors Based on single-cell and spatial RNA sequencing, Zhao et al. depict a comprehensive transcriptomic landscape of the developing mouse stomach and small and large intestine during E9.5–E15.5. This landscape reveals a dynamic cell atlas, uncovers the early regionalization process, and reveals mesenchymal-epithelial interactions regulating critical developmental events and cell fate determination.