Hippo signaling differentially regulates distal progenitor subpopulations and their transitional states to construct the mammalian lungs.

ABSTRACT: Lung size control and cell type specification are key unresolved issues. In this study, we have engineered mosaic patterns of Hippo signaling to reveal the developmental potential of SOX9⁺ progenitors at the distal lung buds. Our results show that the distal SOX9⁺ subdomain is sufficient to direct lung outgrowth through bifurcation, providing a mechanism for lung size control. Through single-cell analyses, we identify transitional cell states and candidates for promoting cell fates. Moreover, genetic analysis reveals that Hippo signaling induces distinct cell fates at different SOX9⁺ subdomains to produce the conducting airways and the alveolar epithelium. These results provide the first map of the developmental paths of lung cells. Some of the developmenta

SUBMITTER: Zhang K 

PROVIDER: S-EPMC12636293 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature