New Insights into Molecular Mechanisms of Lung Development Unveiled

Researchers from the Guangzhou Institutes of Biomedicine and Health, part of the Chinese Academy of Sciences, have developed a detailed spatiotemporal atlas of mouse lung development, uncovering significant molecular and cellular processes involved in pulmonary organogenesis.

Published in Science Bulletin, the study explores gene expression dynamics from embryonic day 12.5 (E12.5) to postnatal day 0 (P0), utilizing advanced high-throughput spatial transcriptomics techniques. Understanding the complex architecture of the lungs, essential for effective gas exchange and susceptible to various environmental factors, is crucial for improving treatments for respiratory diseases.

The research identified ten distinct spatial domains within the developing lung, each linked to specific anatomical structures and cell types. The findings illustrate how the lung's airways form along a proximal-distal axis, characterized by unique gene expression patterns in the proximal (near the trachea) and distal (toward the alveoli) regions. Noteworthy genes, including Sox2 and Foxj1, were found to be more prevalent in the proximal airways, whereas Sox9 and Etv5 were dominant in the distal areas.

Significantly, the study highlighted two alveolar niches (D2 and D7) that displayed differing states of maturation. The D2 niche, marked by increased expression of Angpt2 and Epha3, demonstrated a more advanced maturation level and played a critical role in alveolar formation just prior to birth. Additionally, researchers identified regulatory networks that facilitate regional specialization within the lungs, such as the role of Foxa1 in the development of proximal airways and Tbx2/Cux1 in the maturation of distal airways and alveoli. Active signaling pathways, including VEGF, ANGPT, and EPHA, were associated with mature alveolar niches, indicating their involvement in angiogenesis and tissue remodeling processes.

This comprehensive atlas serves as a valuable resource for investigating lung development and related diseases in humans. By comparing spatial gene expression across species, researchers may identify conserved or unique mechanisms, providing new targets for treating conditions like idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

For further details, refer to the original study: Xiaogao Meng et al., Spatiotemporal transcriptome atlas of developing mouse lung, Science Bulletin (2025). DOI: 10.1016/j.scib.2025.03.012.