Source Data for Wang et al. 2021: Budding Epithelial Morphogenesis Driven by Cell-Matrix vs. Cell-Cell Adhesion

This dataset can be used to reproduce all plots in Wang et al., 2021 titled: "Budding Epithelial Morphogenesis Driven by Cell-Matrix vs. Cell-Cell Adhesion" in combination with the Jupyter notebook scripts available from this Github repository: https://github.com/snownontrace/public-scripts-Wang2020-branching-morphogenesis.git

1. Download and decompress the dataset zip file.

2. Place the "data" folder and the "scripts" folder (from GitHub) in the same folder.

Note: This folder organization is necessary because relative path is used to read in data in all scripts (e.g., '../data/specific_data_folder/data_table').

3. Run scripts to reproduce plots of interest. Refer to the table in the README file of the Github repository to find out which scripts were used to generate which figures.

Abstract:

Many embryonic organs undergo epithelial morphogenesis to form tree-like hierarchical structures. However, it remains unclear what drives the budding and branching of stratified epithelia, such as in embryonic salivary gland and pancreas. Here, we performed live-organ imaging of mouse embryonic salivary glands at single-cell resolution to reveal that budding morphogenesis is driven by expansion and folding of a distinct epithelial surface cell sheet characterized by strong cell-matrix adhesions and weak cell-cell adhesions. Profiling of single-cell transcriptomes of this epithelium revealed spatial patterns of transcription underlying these cell adhesion differences. We then synthetically reconstituted budding morphogenesis by experimentally suppressing E-cadherin expression and inducing basement membrane formation in 3D spheroid cultures of engineered cells, which required β1 integrin-mediated cell-matrix adhesion for successful budding. Thus, stratified epithelial budding, the key first step of branching morphogenesis, is driven by an overall combination of strong cell-matrix adhesion and weak cell-cell adhesion by peripheral epithelial cells.