Multi-omic profiling of DNA damage-induced senescence in healthy and IPF primary human lung fibroblasts [RNA-seq]

While the heterogeneity across cell types is well documented, variation within the same cell type is only beginning to be understood. Here, we show primary, human lung fibroblasts from either donors who are healthy or diagnosed with idiopathic pulmonary fibrosis (IPF) exhibit a subtle form of heterogeneity over time after DNA damage.

Moreover, senescent IPF lung fibroblasts display a dysregulated transcriptional–protein DNA damage response (DDR). Weighted gene correlation network analysis (WGCNA) reveals unique and known targets linking senescent IPF lung fibroblast heterogeneity to genes associated with DNA damage and repair and cytokine and chemokine responses. We combine our healthy and IPF senescent gene expression datasets to develop a novel gene signature of senescence-associated genes that identify disease-relevant cells in human single-cell RNA-seq (scRNA-seq) data.