Fig. 8: Wound priming initiates field cancerization.
From: Tissue memory relies on stem cell priming in distal undamaged areas
a, eSCC onset in wounded (Wd), UVB-treated only (TS) or wounded and UVB-treated (Wd&TS) tail skin. Incidence (top) and representative H&E (bottom). Data are mean ± s.e.m. n = 5 (TS, Wd), n = 22 (Wd&TS). b, Skin section stained with H2AK119ub or γ-H2A.X (top) and quantifications (bottom) in wound bed (Wb), distal memory (Distal 3–7 mm from Wb) and far control (Ctrl >2 cm from Wb) areas. n = 4 (Ctrl), n = 6 (Distal, Wb). c–h, ATAC–seq of sorted Lrig1 GL upper-HF cells (Sca-1+), upon UVB treatment from Distal and Ctrl. c, Density plots depict ATAC–seq signals ±1 kb of deregulated peaks (logFC > 0.5, P < 0.05) (top) and heat map of the signal score of individual peaks (bottom). d, Venn diagram of peaks in Distal versus Ctrl. Distal gained peaks in red. e, Snapshots of genomic loci associated to gained peaks in Distal UVB-treated skin. f, Overlap (red) between the genes associated to gained peaks in Distal UVB-treated skin (respect to Ctrl) and to Distal memory peaks. Random permutation p-value (P) is shown. g, GO analysis of genes associated to gained peaks in Distal versus Ctrl, measured as −log10 of p-value (P). Dashed line underlines significance. h, Transcription factor (TF) motifs enriched in gained peaks Distal versus Ctrl, based on de novo motif discovery. Motifs with a match score of >0.8 to a known motif are ranked. i, Number of tumours. n = 5 (TS), n = 9 (Wd&TS). j, Quantification (left) and skin section staining (right) of H2AK119ub. n = 3 (Ctrl), n = 5 (Distal). k,l, Glut1 expression in Distal or Ctrl area of Wd&TS samples. Skin section images (k) and quantification (l). n = 8 Wd&TS. m, Tumour incidence in vehicle versus PRT4165-treated hairless mice. n = 7 (vehicle), n = 4 (PRT4165). Statistic: Mantel–Cox test. n, H2AK119ub and Glut1 staining on human SCC sections. P-value from a two-tailed t-test, if not differently indicated. Data are mean ± s.d., if not differently indicated. Scale bars: 50 μm (a, b, j, k and n). ATAC–seq (c–h) data are the integration of two independent experiments, each of them based on two biological replicates.
