Highly regional generation and heterogenous differentiation of basal cells in mouse trachea

The airway epithelium comprises three major cell types: basal cells, secretory cells, and ciliated cells. Among these, basal cells serve as stem cells to generate other cell types. Airway basal cells have been recognized as functionally heterogeneous, with numerous studies with specific cell markers. The regional heterogeneity of basal cells has yet to be fully addressed, despite there being some in vitro evidence. In this study, we utilized a proliferation tracing system to demonstrate regional heterogeneity in the proliferative capacity and differentiation of airway basal cells. We found that dorsal basal cells possess a significantly higher proliferative capacity compared to their ventral counterparts. Further analysis revealed that the proliferating basal cells primarily constitute a subset previously identified as multipotent basal stem cells, which undergo symmetric division to expand the stem cell pool. Furthermore, we identified that the canonical Wnt signaling pathway plays a crucial role in maintaining the proliferation of these multipotent basal cells. These findings may have important implications for understanding airway repair mechanisms in disease and injury.