Single Cell and Spatial Transcriptomics Implicate Vascular Cell Orchestration of Inflammatory Changes After Ultraviolet Light Exposure [scRNA-seq]

To elucidate the complex effects of acute UV radiation (UVR) on the skin, we exposed shaved mouse skin to UVB and performed transcriptomic profiling of the epidermis, deep dermis and adipose tissue. Spatial transcriptomic analysis revealed the most pronounced gene expression changes in the epidermis, peaking at 24 hours post-irradiation. While CD45⁺ immune cells showed differential expression of chemokines, cytokines, and acute-phase proteins, cytokeratin⁺ epidermal cells upregulated genes related to cellular stress and damage (e.g., Usp19, Adam25), as well as structural remodeling and apoptosis (e.g., Krt18, Phlda1). Single-cell RNA sequencing (scRNA-seq) conducted 12 hours after UVR exposure identified 4,849 differentially expressed genes (DEGs), with the epidermis and endothelial cells showing the highest DEG counts. Pathway analysis of upregulated genes in the epidermis revealed enrichment in VEGF, HIPPO, complement, IL-6, and apoptosis signaling pathways. In endothelial cells, UVR induced expression of multiple chemokines and cytokines. Notably, receptor-ligand analysis highlighted endothelial cells as key targets of CXCL chemokines and complement component C3. In fibroblasts, UVR triggered upregulation of inflammatory activation markers (Osmr, Cux1) alongside genes associated with glucose metabolism (Hif1a, Pkm). Cross-species comparison of UVR-responsive DEGs between mice and humans revealed strong concordance, particularly in TGF-β and TNF-associated pathways.