Cell-specific expression of lung disease risk-related genes in the human small airway epithelium

• Published in: Respiratory research 2020-07, Vol.21 (1), p.200-200, Article 200
• Main Authors: Zuo, Wu-Lin, Rostami, Mahboubeh R, Shenoy, Shushila A, LeBlanc, Michelle G, Salit, Jacqueline, Strulovici-Barel, Yael, O'Beirne, Sarah L, Kaner, Robert J, Leopold, Philip L, Mezey, Jason G, Schymeinsky, Juergen, Quast, Karsten, Visvanathan, Sudha, Fine, Jay S, Thomas, Matthew J, Crystal, Ronald G
• Format: Article
• Language: English
• Subjects: Antigens; Care and treatment; Cell cycle; Chronic obstructive pulmonary disease; Cigarette smoking; Cystic fibrosis; Defense; Diagnosis; Disorders; Epithelial cells; Epithelium; Fibrosis; Gene expression; Gene sequencing; Genes; Genetic aspects; Genotypes; Health aspects; Health risks; Identification and classification; Immune/inflammatory cells; Inflammation; Inherited and acquired pulmonary disorders; Lung cancer; Lung diseases; Obstructive lung disease; Pathogenesis; Phenotypes; Population; Populations; Respiratory tract; Ribonucleic acid; Risk; RNA; Signal transduction; Single-cell transcriptomes; Smoking; Transcription factors
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-020-01442-9

The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders. Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populations to the risk for lung diseases. Drop-seq single-cell RNA-sequencing was used to characterize the transcriptome of single cells from human SAE of nonsmokers and smokers by bronchoscopic brushing. Eleven distinct cell populations were identified, including major and rare epithelial cells, and immune/inflammatory cells. There was cell type-specific expression of genes relevant to the risk of the inherited pulmonary disorders, genes associated with risk of chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis and (non-mutated) driver genes for lung cancers. Cigarette smoking significantly altered the cell type-specific transcriptomes and disease risk-related genes. This data provides new insights into the possible contribution of specific lung cells to the pathogenesis of lung disorders.