scRNA-seq and scATAC-seq analyses highlight the role of TNF signaling in chronic obstructive pulmonary disease progression

Abstract

Chronic obstructive pulmonary disease (COPD) is a prevalent and progressive form of respiratory disease in which patients exhibit persistent respiratory damage affecting the alveoli and/or airway due to exposure to toxic gases or particulate matter. The best-studied risk factor associated with COPD incidence is cigarette smoke. C57BL/6 mice were exposed to cigarette smoke and lipopolysaccharide to establish a COPD model, followed by scATAC sequencing and scRNA sequencing of lung tissue samples. The resultant data revealed consistent findings between scATAC-seq and scRNA-seq regarding cell types, differentially expressed genes, and signaling pathways. Tumor necrosis factor (TNF) signaling pathway enrichment was evident in the scRNA-seq and scATAC-seq datasets, with similar trends in monocytes/macrophages, dendritic cells, and B cells. Significant TNFR1 upregulation and high levels of activity related to cellular communication were observed, and significant increases in IL1B, CSF1, and BCL3 site accessibility were evident in cells from COPD model mice. Overall, these findings suggested that the TNF signaling pathway plays roles in the differentiation of monocytes and macrophages, the promotion of T cell proliferation, and the induction of airway inflammation that ultimately drives COPD progression.