Heterogeneity in B- and epithelial-cell senescence in the pathogenesis of COPD/emphysema [Xenium]

However, the cell-specific changes resulting in ‘senescent microenvironment’ in COPD remains elusive. To bridge this gap, we used single-cell multiomics approach to identify the differentially regulated cell types, genes/pathways and spatial organization of senescence phenotype in smoke-induced emphysema in humans.

Dimensionality reduction and clustering of 121,885 cells in lung tissues from emphysematous COPD patients and healthy controls (n = 6/ group) with and without a smoking history revealed a significant enrichment (p<0.01) in the senescence associated gene sets in B-lymphocytes and multi-ciliated non-nasal (MNN) epithelial cell clusters from COPD patients. Senescent B cells were found to have dysfunctional development and maturation as denoted by alterations in expression of targets including BMP6, CCNB2, MCM4, PTEN and DDIT4 in diseased state.