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Hu, Y.* ; Hu, Q.* ; Ansari, M. ; Riemondy, K.* ; Pineda, R.H.* ; Sembrat, J.* ; Leme, A.S.* ; Ngo, K.* ; Morgenthaler, O.* ; Ha, K.* ; Gao, B.* ; Janssen, W.J.* ; Basil, M.C.* ; Kliment, C.R.* ; Morrisey, E.* ; Lehmann, M. ; Evans, C.M.* ; Schiller, H. ; Königshoff, M.*

Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD.

Eur. Respir. J. 64:2302071 (2024)

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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

Corresponding Author

Keywords Migration Inhibitory Factor; Stem-cells; Lung; Maintenance; Activation; Pathways; Elastase

ISSN (print) / ISBN 0903-1936

e-ISSN 1399-3003

Journal European Respiratory Journal

Quellenangaben Volume: 64, Issue: 6, Article Number: 2302071

Publisher European Respiratory Society

Publishing Place Sheffield

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) German Center for Lung Research (DZL)
Institute of Lung Health and Immunity (LHI)

Grants Burroughs Wellcome Fund Career Award for Medical Scientists
VA Merit
LongFonds Accelerate BREATH Program
Helmholtz Association
European Union
Chan Zuckerberg Initiative
Burroughs Wellcome Fund -Career Award for Medical Scientists (CAMS)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
(BfR)
NIH NHLBI