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Mouse Embryonic Lung Culture, A System to Evaluate the Molecular Mechanisms of Branching
Published on: June 30, 2010
Spatiotemporal Profiling Defines the Epithelial and Mesenchymal Transition Window in Embryonic Lung Morphogenesis
Huiwen Zheng1,2, Jinpei Lin1,2, Hanyi Li3
1College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Journal of Developmental Biology
|June 25, 2026
Summary
This study maps embryonic lung development, revealing a key transition at E13.5 where progenitor cells mature. It links developmental gene programs to lung cancer, finding embryonic features in tumors.
Area of Science:
- Developmental Biology
- Genomics
- Computational Biology
Background:
- Lung organogenesis involves complex epithelial-mesenchymal interactions, but the gene regulatory programs governing the pseudoglandular stage are not fully understood.
- Existing methods lack resolution for detailed cell-type analysis in spatial transcriptomic data during embryonic lung development.
Purpose of the Study:
- To systematically characterize epithelial and mesenchymal dynamics during embryonic lung development using integrated spatial and single-cell transcriptomics.
- To construct a 3D spatiotemporal landscape of lung development and identify key regulatory mechanisms.
- To link embryonic lung developmental programs with lung cancer-related features.
Main Methods:
- Integrated spatial and single-cell transcriptomic data across embryonic developmental stages.
- Developed a bin-based deconvolution strategy for high-precision cell-type assignment in spatial transcriptomics.
- Analyzed transcription factor module activity, intercellular communication, and integrated genome-wide association study (GWAS) data.
Main Results:
- Constructed a 3D spatiotemporal landscape of lung development, revealing stage-specific functional heterogeneity.
- Identified E13.5 as a critical transition window for progenitor cell maturation and epithelial-mesenchymal interactions.
- Discovered temporally coordinated transcription factor modules (e.g., Tbx3, Tbx5, Gli1) orchestrating lung morphogenesis.
- Linked embryonic lung progenitor states to lung cancer transcriptional programs, particularly epithelial-mesenchymal plasticity and RNA splicing.
- Observed embryonic-like molecular features in TP53/HNRNP-mutant lung adenocarcinomas.
Conclusions:
- Provided a spatiotemporally resolved framework for embryonic lung development.
- Identified a critical transition window linking lung morphogenesis, regulatory network remodeling, and cancer-associated epithelial plasticity.
- Established a connection between embryonic developmental programs and lung cancer pathogenesis.
