Wnt/?-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema.

ABSTRACT: Wnt/?-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/?-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/?-catenin responsive progenitor cells and the potential impact of Wnt/?-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used TCF/Lef:H2B/GFP reporter mice to investigate the role of Wnt/?-catenin signaling in lung organoid formation. We identified an organoid-forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/?-catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt/?-catenin activity was required for the initiation of multiple subtypes of distal lung organoids derived from the Wnt^low epithelial progenitors. Further ectopic Wnt/?-catenin activation specifically led to an increase in alveolar organoid number; however, the subsequent proliferation of alveolar epithelial cells in the organoids did not require constitutive Wnt/?-catenin signaling. Distal lung epithelial progenitor cells derived from the mouse model of elastase-induced emphysema exhibited reduced organoid forming capacity. This was rescued by Wnt/?-catenin signal activation, which largely increased the number of alveolar organoids. Together, our study reveals a novel mechanism of lung epithelial progenitor cell activation in homeostasis and emphysema.

SUBMITTER: Hu Y 

PROVIDER: S-EPMC7116441 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature