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Wnt/β-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema.
Stem Cells 38, 1467-1478 (2020)
Wnt/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 organoid 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 of multiple subtypes of distal lung organoids derived from the Wntlow epithelial progenitors. Further ectopic Wnt/β-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/β-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/β-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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Chronic Lung Disease ; Emphysema ; Lung Epithelial Progenitor ; Organoid ; Regeneration ; Wnt/β-catenin; Gene Set Enrichment; Stem-cells; Alveolar; Repair; Airway; Activation; Population
ISSN (print) / ISBN
0737-1454
e-ISSN
1549-4918
Journal
Stem Cells
Quellenangaben
Volume: 38,
Issue: 11,
Pages: 1467-1478
Publisher
Wiley
Publishing Place
111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Lung Repair and Regeneration (LRR)