Fig. 1.

Schematics of scRNAs analyses. Lung tissue samples were from 3 COPD patients (COPD), 3 age-matched controls (control old), and 3 young individuals (control young), among which 4 were active smokers (AS) and 5 were never-smokers (NS). Upon dissociation and barcoding, scRNA-seq was carried out. Following data deconvolution with a linear mixed model, cell type prioritization analysis was performed under 3 different pathological conditions, including COPD, aging, and smoking, to identify the most affected cell types under each condition (the biggest colored cell type). By causality analysis between the prioritized cell types with other cell types, cell type level alterations were integrated into 3 condition-specific system-level malfunctions, of which the one under COPD condition was defined as “COPD core” pathology. Finally, a new comprehensive COPD pathological model taking aging and smoking into account was established by combining system-level malfunctions under all conditions