Characterization of the COPD alveolar niche using single-cell RNA sequencing.

Autor: Sauler M; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA. maor.sauler@yale.edu., McDonough JE; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA. john.e.mcdonough@yale.edu., Adams TS; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Kothapalli N; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Barnthaler T; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.; Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria., Werder RB; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, 02118, USA.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA.; QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia., Schupp JC; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), Hannover, Germany., Nouws J; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Robertson MJ; Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA., Coarfa C; Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA., Yang T; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.; Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Chioccioli M; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Omote N; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Cosme C Jr; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Poli S; Department of Internal Medicine, Mount Sinai Medical Center, Miami, FL, USA., Ayaub EA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Chu SG; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jensen KH; Intomics A/S, Lyngby, Denmark., Gomez JL; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Britto CJ; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Raredon MSB; Department of Biomedical Engineering, Yale University, New Haven, CT, USA.; Medical Scientist Training Program, Yale School of Medicine, New Haven, CT, USA., Niklason LE; Department of Biomedical Engineering, Yale University, New Haven, CT, USA., Wilson AA; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA, 02118, USA.; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA., Timshel PN; Intomics A/S, Lyngby, Denmark., Kaminski N; Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Rosas IO; Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jan 25; Vol. 13 (1), pp. 494. Date of Electronic Publication: 2022 Jan 25.
DOI: 10.1038/s41467-022-28062-9
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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