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Wnt/β-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2020 Nov; Vol. 38 (11), pp. 1467-1478. Date of Electronic Publication: 2020 Jun 18. - Publication Year :
- 2020
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Abstract
- 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 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 Wnt <superscript>low</superscript> 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.<br /> (©2020 The Authors. Stem Cells published by Wiley Periodicals LLC on behalf of AlphaMed Press 2020.)
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 38
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 32526076
- Full Text :
- https://doi.org/10.1002/stem.3241