Mesenchymal-epithelial interaction regulates gastrointestinal tract development in mouse embryos
Lianzheng Zhao1, Wanlu Song1, Ye-Guang Chen2
1The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Cell Reports
|July 13, 2022
Summary
This study maps mouse stomach and intestine development using advanced sequencing. It reveals how early cell populations and interactions guide organ formation and reveals that niche factors can alter cell fate.
Area of Science:
- Developmental Biology
- Genomics
- Gastroenterology
Background:
- Cellular and molecular changes during stomach and intestine development post-embryonic gut tube patterning are poorly understood.
- Existing knowledge gaps hinder a comprehensive understanding of gastrointestinal organogenesis.
Purpose of the Study:
- To construct a detailed spatiotemporal transcriptomic landscape of the developing mouse stomach and intestine.
- To identify distinct cell subpopulations and analyze mesenchymal-epithelial interactions during embryonic development.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) and spatial RNA sequencing (sRNA-seq) were employed.
- Analysis spanned embryonic days E9.5 to E15.5 in mouse models.
- Gut tube-derived organoids were utilized to investigate cell fate plasticity.
Main Results:
- Identification of specific mesenchymal subpopulations (Lox+, Aldh1a3+, Adamdec1+).
- Tracing of epithelial and mesenchymal regionalization and heterogeneity back to E9.5.
- Demonstration of coordinated mesenchymal-epithelial development driving stomach regionalization, intestine segmentation, and villus formation.
- Evidence that niche factors like fibroblast growth factors (FGFs) and retinoic acid (RA) can switch foregut and hindgut cell fates.
Conclusions:
- This research provides a foundational transcriptomic atlas for early gastrointestinal development.
- Coordinated interactions between epithelium and mesenchyme are crucial for proper organ formation.
- The plasticity of cell fate in response to niche factors offers insights into developmental regulation.
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