Characterization of Cell Type Abundance and Gene Expression Timeline from Burned Skin Bulk Transcriptomics by Deconvolution

Abstract

Currently, no timeline of cell heterogeneity in thermally injured skin has been reported. In this study, we proposed an approach to deconvoluting cell type abundance and expression from skin bulk transcriptomics with cell type signature matrix constructed by combining independent normal skin and peripheral blood scRNA-seq datasets. Using CIBERSORTx group mode deconvolution, we identified perturbed cell type fractions and cell-type specific gene expression in three stages postthermal injury. We found an increase in cell proportions and cell type specific gene expression perturbation of neutrophils, macrophages, and endothelial cells and a decrease in CD4+ T cells, keratinocytes, melanocyte and fibroblast cells, and cell type specific gene expression perturbation post burn injury. Keratinocyte, fibroblast and macrophage up regulated genes were dynamically enriched in overlapping and distinct GO biological processes including acute phase response, leukocyte migration, metabolic, morphogenesis and development process. Down regulated genes were enriched in Wnt signaling, mesenchymal cell differentiation, gland and axon development, epidermal morphogenesis, fatty acid and glucose metabolic process. We noticed an increase in CCL7, CCL2, CCL20, CCR1, CCR5, CCXL8, CXCL2, CXCL3, MMP1, MMP8, MMP3, IL24, IL6, IL1B, IL18R1 and TGFBR1 and a decrease in CCL27, CCR10, CCR6, CCR8, CXCL9, IL37, IL17, IL7, IL11R, IL17R, TGFBR3, FGFR1-4, and IGFR1 in keratinocytes and/or fibroblasts. The inferred timeline of wound healing and CC and CXC genes in keratinocyte was validated on independent dataset GSE174661 of purified keratinocytes. The timeline of different cell types post burn may facilitate therapeutic timing.