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

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...

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Bibliographic Details
Published in:Nature communications 2022-01, Vol.13 (1), p.494-494, Article 494
Main Authors: Sauler, Maor, McDonough, John E., Adams, Taylor S., Kothapalli, Neeharika, Barnthaler, Thomas, Werder, Rhiannon B., Schupp, Jonas C., Nouws, Jessica, Robertson, Matthew J., Coarfa, Cristian, Yang, Tao, Chioccioli, Maurizio, Omote, Norihito, Cosme, Carlos, Poli, Sergio, Ayaub, Ehab A., Chu, Sarah G., Jensen, Klaus H., Gomez, Jose L., Britto, Clemente J., Raredon, Micha Sam B., Niklason, Laura E., Wilson, Andrew A., Timshel, Pascal N., Kaminski, Naftali, Rosas, Ivan O.
Format: Article
Language:English
Subjects:
38
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49/91
631/114/2391
631/1647/514/1949
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692/699/1785/4037
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A549 Cells
Alveolar Epithelial Cells - classification
Alveolar Epithelial Cells - metabolism
Alveoli
Animals
Cell culture
Cells, Cultured
Cellular stress response
Chemokines
Chronic obstructive pulmonary disease
Cigarette smoke
Cluster Analysis
Endothelial cells
Epithelial cells
Epithelial Cells - metabolism
Epithelium
Female
Gene Expression Profiling - methods
Gene Regulatory Networks
Gene sequencing
Human performance
Humanities and Social Sciences
Humans
Hybridization
Inflammation
Lung - cytology
Lung - metabolism
Lung diseases
Lungs
Macrophages
Male
Metabolism
Metallothionein
Mice
Mice, Inbred C57BL
Mice, Transgenic
multidisciplinary
Obstructive lung disease
Pulmonary Disease, Chronic Obstructive - genetics
Pulmonary Disease, Chronic Obstructive - pathology
Ribonucleic acid
RNA
RNA-Seq - methods
Science
Science (multidisciplinary)
Signal Transduction - genetics
Single-Cell Analysis - methods
Tissues
Transcription
Transcriptomics
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Description
Summary: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. Chronic obstructive pulmonary disease is a leading cause of death worldwide, while our understanding of cell-specific mechanisms underlying its pathobiology remains incomplete. Here the authors perform scRNA-seq of human lung tissue to identify transcriptional changes in alveolar niche cells associated with the disease.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-28062-9