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Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD.
Eur. Respir. J. 64, DOI: 10.1183/13993003.02071-2023 (2024)
Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of chronic obstructive pulmonary disease (COPD) that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific sub-population of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single cell RNA-seq and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C (SPC) and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII sub-population derived from club cells was also identified in mouse COPD models using lineage labeling. Human and mouse ATII sub-populations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0903-1936
e-ISSN
1399-3003
Journal
European Respiratory Journal
Quellenangaben
Volume: 64,
Issue: 6
Publisher
European Respiratory Society
Publishing Place
Sheffield
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Lung Health and Immunity (LHI)