Researchers from the Guangzhou Institutes of Biomedicine and Health of the Chinese Academy of Sciences have recently unveiled a groundbreaking study that sheds light on the molecular and cellular mechanisms driving pulmonary organogenesis. By constructing a comprehensive spatiotemporal atlas of developing mouse lungs, the research team has provided invaluable insights into the intricate processes underlying lung development.
Published in Science Bulletin, the study utilized high-throughput spatial transcriptomics to analyze gene expression dynamics at key developmental stages, ranging from embryonic day 12.5 to birth. The lungs, responsible for crucial gas exchange functions and susceptible to various environmental factors, require a deep understanding of their development to enhance the treatment of respiratory diseases.
Through the spatial transcriptomic mapping of gene expression patterns in developing mouse lungs, the researchers identified 10 distinct spatial domains, each corresponding to specific anatomical structures and cell types within the lung. The study revealed the developmental trajectory of the lung’s airways along a proximal-distal axis, showcasing unique gene expression patterns in proximal and distal regions. Genes like Sox2 and Foxj1 were found to be enriched in proximal airways, while Sox9 and Etv5 were more prominent in distal regions.
Moreover, the researchers identified two alveolar niches (D2 and D7) with differing maturation states, shedding light on the regulatory networks driving regional specialization. Key signaling pathways such as VEGF, ANGPT, and EPHA were found to be highly active in mature alveolar niches, suggesting their role in angiogenesis and tissue remodeling.
This spatiotemporal atlas of developing mouse lungs serves as a foundational resource for investigating human lung development and disease. By comparing spatial gene expression across different species, researchers may uncover conserved or species-specific mechanisms, potentially leading to the development of new therapeutic targets for conditions like idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.
The study, led by Xiaogao Meng et al., was published in Science Bulletin and can be accessed via DOI: 10.1016/j.scib.2025.03.012. This research not only advances our understanding of pulmonary organogenesis but also opens up new avenues for the treatment of respiratory conditions.
