Meta-analysis of single-cell RNA-sequencing data for depicting the transcriptomic landscape of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by airflow limitation and chronic inflammation of the lungs that is a leading cause of death worldwide. Since the complete pathological mechanisms at the single-cell level are not fully understood yet, an integrative approach to characterizing the single-cell-resolution landscape of COPD is required. To identify the cell types and mechanisms associated with the development of COPD, we conducted a meta-analysis using three single-cell RNA-sequencing datasets of COPD. Among the 154,011 cells from 16 COPD patients and 18 healthy subjects, 17 distinct cell types were observed. Of the 17 cell types, monocytes, mast cells, and alveolar type 2 cells (AT2 cells) were found to be etiologically implicated in COPD based on genetic and transcriptomic features. The most transcriptomically diversified states of the three etiological cell types showed significant enrichment in immune/inflammatory responses (monocytes and mast cells) and/or mitochondrial dysfunction (monocytes and AT2 cells). We then identified three chemical candidates that may potentially induce COPD by modulating gene expression patterns in the three etiological cell types. Overall, our study suggests the single-cell level mechanisms underlying the pathogenesis of COPD and may provide information on toxic compounds that could be potential risk factors for COPD.

Keywords: Alveolar type 2 cells; Chronic obstructive pulmonary disease; Mast cells; Meta-analysis; Monocytes; Single-cell RNA-sequencing.