Cell Reports
Volume 40, Issue 2, 12 July 2022, 111053
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Article
Mesenchymal-epithelial interaction regulates gastrointestinal tract development in mouse embryos

https://doi.org/10.1016/j.celrep.2022.111053Get rights and content
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Highlights

  • 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

Summary

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.

Research topic(s)

CP: Developmental biology

Keywords

stomach
intestine
development
single-cell RNA-seq
spatial RNA-seq
mesenchymal-epithelial interaction

Data and code availability

  • Single-cell and bulk RNA-seq data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Microscopy data reported in this paper will be shared by the lead contact upon request.

  • All original code has been deposited at GitHub and is publicly available as of the date of publication. DOIs are listed in the key resources table.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

3

These authors contributed equally

4

Lead contact