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

Stem Cells
Yan HuMelanie Königshoff

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 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 c...Continue Reading

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Citations

Nov 6, 2020·Nature·Thomas M ConlonAli Önder Yildirim
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Zhao Ni Wang, Xiao Xiao Tang
Feb 1, 2021·Stem Cell Research & Therapy·Jing KongFukai Bao
Jun 10, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anthony TamChinten James Lim
Sep 4, 2021·European Journal of Pharmacology·Siddhi JainPawan Sharma
Jun 10, 2021·American Journal of Respiratory Cell and Molecular Biology·Tianju LiuSem H Phan

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Datasets Mentioned

BETA
GSE47460
37

Methods Mentioned

BETA
flow cytometry

Software Mentioned

stats
GAGE
R
R studio

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