Researchers reveal new molecular and cellular mechanisms underlying pulmonary organogenesis microbiologystudy

A research team led by the Guangzhou Institutes of Biomedicine and Health of the Chinese Academy of Sciences has constructed a comprehensive spatiotemporal atlas of developing mouse lungs, revealing new molecular and cellular mechanisms underlying pulmonary organogenesis.

The study, published in Science Bulletin, delineates gene expression dynamics across key developmental stages—from embryonic day 12.5 (E12.5) to birth (postnatal day 0, P0)—using high-throughput spatial transcriptomics.

The lung’s intricate architecture, critical for gas exchange and vulnerable to environmental insults, makes understanding its development essential for advancing treatments for respiratory diseases.

This study employs high-throughput spatial transcriptomics to map gene expression patterns in developing mouse lungs. The researchers identified 10 distinct spatial domains, each corresponding to different anatomical structures and cell types within the lung.

The findings reveal how the lung’s airways develop along a proximal-distal axis, with distinct gene expression patterns characterizing the proximal (closer to the trachea) and distal (toward the alveoli) regions. Genes such as Sox2 and Foxj1 are enriched in the proximal airways, while Sox9 and Etv5 are more prominent in the distal regions.

Notably, two alveolar niches (D2 and D7) exhibited divergent maturation states. D2, associated with elevated Angpt2 and Epha3 expression, displayed advanced maturation and was pivotal for alveolar formation near birth. The study further uncovered regulatory networks driving regional specialization, including Foxa1 in proximal airway development and Tbx2/Cux1 in distal airway and alveolar maturation. Key signaling pathways (VEGF, ANGPT, EPHA) were highly active in mature alveolar niches, implicating their roles in angiogenesis and tissue remodeling.

This atlas provides a foundational resource for probing human lung development and disease. Cross-species comparisons of spatial gene expression could reveal conserved or species-specific mechanisms, offering novel targets for conditions like idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.