Fig. 1. UVR-driven mutations in adult donor dermal fibroblasts correlate with ECM degradation and collagenase expression.

a Volcano plot gene expression and b extracellular matrix (ECM) heatmap by COSMIC signature 7 mutations in skin fibroblasts²³. Colour scale: red upregulated, blue downregulated genes, sample clustered by signature 7 mutations: colour scale 0 (white) to 112 (green), red box: genes upregulated with signature 7 mutations. c Atomic force microscopy (scale: 5 µm, height colour scale −115 (dark brown), 115 (white)), and d matrix roughness (Rq) of in vitro ECM of HFF and UV-HFF, two-sided Mann–Whitney U *p = 0.0286, data represents two measurements from two biologically independent cell lines per condition. e Quantification of fibre alignment distribution in human foreskin fibroblasts HFF and UV-HFF-derived ECM by fibronectin immunofluorescence. f Fraction of fibres within 10° of mode orientation, two-sided Mann–Whitney U **p = 0.0022, data represents two biologically independent cell lines three fields of view per condition. g Immunofluorescence of fibronectin fibres in decellularised HFF and UV-HFF-derived ECM, colour coded for orientation of fibre, cyan represents mode, red ±90°, scale bar: 25 µm. h Masson’s trichrome collagen stain of sun-protected (n = 9, noCSD) and sun-damaged (n = 7, CSD) dermis, two-sided Mann–Whitney U ****p < 0.0001. i Correlation between SNV load and solar elastosis in fibroblasts, blue: CSD, pink: noCSD, two-sided Spearman correlation R = 0.40, p = 0.2, n = 13 biologically independent samples. Error bars: standard error of the mean (bar).