Early emergence of inter-lobar heterogeneity in mouse embryonic lung.

The mammalian lung is organized into anatomically distinct lobes, yet whether regional heterogeneity arises among different lobes remains poorly understood. Here, we performed comprehensive transcriptomic profiling of individual lung lobes at the pseudoglandular stage. Comparative analyses revealed that consistent inter-lobar divergence occurs primarily at the level of protein-coding genes. Notably, the left lung lobe exhibits enrichment of immune-response-associated gene expression and increased abundance of early general capillary (gCap) endothelial cells, whereas the right cranial lobe preferentially expresses genes associated with ventricular cardiac muscle morphogenesis and shows reduced gCap enrichment. Integration with publicly available datasets and experimental validation further confirmed the heterogeneous distribution of gCap cells. Together, our findings indicate that molecular and cellular inter-lobar heterogeneity emerges during embryonic development and highlight the significance of considering lobe identity in understanding pulmonary development and related congenital diseases.