Wnt/ β‐catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema

Wnt/ β‐catenin signaling supports alveolar, bronchiolar, and bronchioalveolar organoids formation from distal lung epithelial progenitors of healthy lungs. In emphysema, a chronic lung disease characterized by distal tissue destruction and reduction of Wnt/β‐catenin activity, distal lung epithelial progenitors are impaired and form fewer alveolar organoids. Activation of Wnt/β‐catenin signaling rescues alveolar organoid formation, thus revealing a novel mechanism of lung epithelial progenitor cell activation in emphysema. AbstractWnt/ β‐catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/β‐catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt /β‐catenin responsive progenitor cells and the potential impact of Wnt/β‐catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used a TCF/Lef:H2B/GFP reporter mice to investigate the role of Wnt/β‐catenin signaling in lung or ganoid formation. We identified an organoid‐forming adult distal lung epithelial progenitor cell population characterized by a low Wnt/β‐catenin activity, which was enriched in club and alveolar epithelial type (AT)II cells. Endogenous Wnt/β‐catenin activity was required for the initiation o f multiple subtypes of distal lung organoids de...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research