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Visualizing the codevelopment of structural and immune cells in the human fetal lung using imaging mass cytometry
Li Jia1,2,3, Susana M Chuva De Sousa Lopes4, Vincent van Unen1
1Department of Immunology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
American Journal of Physiology. Lung Cellular and Molecular Physiology
|November 14, 2025
Summary
This study visualizes fetal lung development using imaging mass cytometry, revealing interactions between structural and immune cells. These findings highlight immune-structural cross talk crucial for human lung maturation.
Area of Science:
- Developmental Biology
- Immunology
- Cell Biology
Background:
- Human fetal lung development involves complex interactions between structural and immune cells.
- Understanding these interactions is crucial for identifying developmental defects and potential therapeutic targets.
Purpose of the Study:
- To visualize and map the codevelopment of structural and immune cells in the human fetal lung.
- To investigate the spatial relationships and potential interactions between these cell types during lung organogenesis.
Main Methods:
- Imaging mass cytometry (IMC) with a 31-antibody panel was employed.
- Human fetal lung tissue from postconception weeks 6 to 18 was analyzed.
- Spatial mapping of epithelial, endothelial, and myeloid cell populations was performed.
Main Results:
- Keratin-8 (KRT8+) epithelial structures and α-smooth muscle actin+ cells formed the developing lung architecture.
- Immune cells were predominantly myeloid, with macrophages present early and HLA-DR+ myeloid cells appearing later.
- HLA-DR+ cells were found near KRT8+EpCAM+ structural regions, indicating potential immune-structural interactions.
Conclusions:
- The study provides a detailed protocol for visualizing fetal lung cell codevelopment using IMC.
- Immune-structural cross talk is suggested to play a role in human fetal lung development and maturation.
- IMC enables visualization of spatial relationships crucial for understanding lung development.

