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

• Published in: Nature communications Vol. 13; no. 1; pp. 494 - 17
• 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 49/1; 49/31; 49/91; 631/114/2391; 631/1647/514/1949; 631/80/304; 64/60; 692/308/575; 692/699/1785/4037; 96/2; 96/63; 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; 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; Transcription; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28062-9

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.