Publication Date
1-25-2022
Journal
Nature Communications
DOI
10.1038/s41467-022-28062-9
PMID
35078977
PMCID
PMC8789871
PubMedCentral® Posted Date
1-25-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
A549 Cells, Alveolar Epithelial Cells, Animals, Cells, Cultured, Cluster Analysis, Epithelial Cells, Female, Gene Expression Profiling, Gene Regulatory Networks, Humans, Lung, Male, Mice, Inbred C57BL, Mice, Transgenic, Pulmonary Disease, Chronic Obstructive, RNA-Seq, Signal Transduction, Single-Cell Analysis, Mice
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.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Medical Specialties Commons
Comments
Associated Data