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

Autor:	Hu Y; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Hu Q; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Ansari M; Comprehensive Pneumology Center (CPC)/Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Riemondy K; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA., Pineda R; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Sembrat J; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Leme AS; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Ngo K; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Morgenthaler O; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Ha K; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Gao B; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA., Janssen WJ; Department of Medicine, National Jewish Health, Denver, CO, USA., Basil MC; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA., Kliment CR; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Morrisey E; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lehmann M; Comprehensive Pneumology Center (CPC)/Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.; Institute for Lung Research, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany., Evans CM; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.; Co-senior authors., Schiller HB; Research Unit Precision Regenerative Medicine (PRM), Helmholtz Munich, Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research (DZL), Munich, Germany.; Co-senior authors., Königshoff M; Center for Lung Aging and Regeneration (CLAR), Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA koenigshoffm@upmc.edu.; Geriatric Research Education and Clinical Center (GRECC) at the VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.; Co-senior authors.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2024 Dec 05; Vol. 64 (6). Date of Electronic Publication: 2024 Dec 05 (Print Publication: 2024).
DOI:	10.1183/13993003.02071-2023
Abstrakt:	Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of 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 subpopulation of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single-cell RNA sequencing and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII subpopulation derived from club cells was also identified in mouse COPD models using lineage labelling. Human and mouse ATII subpopulations 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. Competing Interests: Conflict of interest: C.M. Evans reports grants from Cystic Fibrosis Foundation, Department of Defense, and Enterprise Therapeutics, outside the submitted work, and royalties from Eleven P15 consulting. C.R. Kliment serves on an advisory board of Verona Pharmaceuticals. The remaining authors have no conflicts of interest. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu