Year: 2022
Type: article
Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, however our understanding of cell specific mechanisms underlying COPD pathobiology remains incomplete. Here, we analyze single-cell RNA sequencing profiles of explanted lung tissue from subjects with advanced COPD or control lungs, and we validate findings using single-cell RNA sequencing of lungs from mice exposed to 10 months of cigarette smoke, RNA sequencing of isolated human alveolar epithelial cells, functional in vitro models, and in situ hybridization and immunostaining of human lung tissue samples. We identify a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance in COPD. Using transcriptomic network analyses, we predict capillary endothelial cells are inflamed in COPD, particularly through increased CXCL-motif chemokine signaling. Finally, we detect a high-metallothionein expressing macrophage subpopulation enriched in advanced COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD.
Source: Nature Communications
Authors: Maor Sauler, John E. McDonough, Taylor S. Adams, Neeharika Kothapalli, Thomas Barnthaler, Rhiannon B. Werder, Jonas C. Schupp, Jessica Nouws, Matthew J. Robertson, Cristian Coarfa, Tao Yang, Maurizio Chioccioli, Norihito Omote, Carlos Cosme, Sergio Poli, Ehab A. Ayaub, Sarah G. Chu, Klaus H. Jensen, Jose L. Gomez, Clemente J. Britto, Micha Sam B. Raredon, Laura E. Niklason, Andrew A. Wilson, Pascal N. Timshel, Naftali Kaminski, Ivan O. Rosas
Institutions: Yale University, Medical University of Graz, Boston University, Boston Medical Center, QIMR Berghofer Medical Research Institute, Medizinische Hochschule Hannover, German Center for Lung Research, Baylor College of Medicine, The Affiliated Yongchuan Hospital of Chongqing Medical University, Mount Sinai Medical Center, Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Yale University, Flight Attendant Medical Research Institute, Deutsche Forschungsgemeinschaft, Austrian Science Fund, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences
Awards: Thyroid hormone agonism in acute lung injury, G2624223681, IDENTIFYING REVERSIBLE MOLECULAR NETWORKS IN HUMAN PULMONARY FIBROSIS USING SINGLE NUCLEAR TRANSCRIPTOMICS AND SYSTEMS BIOLOGY, Reverse Engineering the Pulmonary Microvasculature, G3842720522, Epithelial Protective Effects of Thyroid Hormone Signaling in Fibrosis, G4119534169, MIF and DNA repair in the emphysematous lung, Engineered Tracheal Replacements, Regulation of Neutrophilic Airway Inflammation by miR-223-3p, G5850682332, Use of the Src Family Kinase Inhibitor Saracatinib in the Treatment of Pulmonary Fibrosis, G6881567127, Systems Biology of a MicroRNA Network in Neutrophilic Asthma, G7334788883, Normal Aging Lung Cell Atlas (NALCA), Role of MIF and CD74 in the pathogenesis of emphysema, Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers, Genomic Analysis of Tissue and Cellular Heterogeneity in IPF, Yale Clinical and Translational Science Award, Air pollution disrupts Inflammasome Regulation in HEart And Lung Total Health (AIRHEALTH), Claude D. Pepper Older Americans Independence Center at Yale, G939619216
OpenAlex ID: W4210263666