Journal article
Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease
npj Regenerative medicine, Vol.9(1), pp.2-14
01/05/2024
DOI: 10.1038/s41536-023-00344-w
PMCID: PMC10770358
PMID: 38182591
Abstract
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.
Details
- Title: Subtitle
- Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease
- Creators
- Kazushige Shiraishi - University of PennsylvaniaMichael P. Morley - University of PennsylvaniaDakota L. Jones - University of PennsylvaniaGan Zhao - University of PennsylvaniaAaron I. Weiner - University of PennsylvaniaMaria C. Basil - University of PennsylvaniaEdward Cantu - University of PennsylvaniaLaura T. Ferguson - University of PennsylvaniaMichele Oyster - University of PennsylvaniaApoorva Babu - University of PennsylvaniaYun Ying - University of PennsylvaniaSu Zhou - University of PennsylvaniaShanru Li - University of PennsylvaniaAndrew E. Vaughan - University of PennsylvaniaEdward E. Morrisey - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- npj Regenerative medicine, Vol.9(1), pp.2-14
- DOI
- 10.1038/s41536-023-00344-w
- PMID
- 38182591
- PMCID
- PMC10770358
- NLM abbreviation
- NPJ Regen Med
- ISSN
- 2057-3995
- eISSN
- 2057-3995
- Publisher
- Nature Publishing Group UK
- Grant note
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) (https://doi.org/10.13039/100000050) Astellas Foundation for Research on Metabolic Disorders (https://doi.org/10.13039/501100007263) U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) Uehara Memorial Foundation (https://doi.org/10.13039/100008732)
- Language
- English
- Date published
- 01/05/2024
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984949262902771
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