Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease

Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplasti...

Full description

Saved in:
Bibliographic Details
Published in:npj Regenerative medicine 2024-01, Vol.9 (1), p.2-2, Article 2
Main Authors: Shiraishi, Kazushige, Morley, Michael P., Jones, Dakota L., Zhao, Gan, Weiner, Aaron I., Basil, Maria C., Cantu, Edward, Ferguson, Laura T., Oyster, Michele, Babu, Apoorva, Ying, Yun, Zhou, Su, Li, Shanru, Vaughan, Andrew E., Morrisey, Edward E.
Format: Article
Language:English
Subjects:
631/532/1360
631/532/489
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cell Biology
Homeostasis
Immunology
Regenerative Medicine/Tissue Engineering
Stem Cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.
ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-023-00344-w