Fig. 2: BD and cSCC show two major CAF subtypes with different functions and a probable origin in distinct dermal fibroblasts.

a UMAP plot visualizing the two main CAF populations. b Top 10 terms from a Gene Ontology (GO) analysis with the most representative expressed genes of each CAF population. Terms are ordered according to p-value, determined by the Fisher’s Exact test. c Bar plot depicting the average proportions of cutaneous iCAFs and myCAFs in BD and cSCC. Bars indicate mean values and each dot represents an analyzed scRNA-seq sample (BD: n = 3 patients, cSCC: n = 5 patients). Statistical analyses of the differences were performed using paired/unpaired t-tests and error bars represent the standard deviation. d Violin plots showing the average gene expression of the known gene signatures corresponding to the four previously defined fibroblast subpopulations27 in cutaneous iCAFs and myCAFs. Statistical analyses were performed using a two-sided Wilcoxon Rank Sum test (pro-inflammatory: p value < 2.2e-16, secretory-reticular: p value = 1.506e-09, mesenchymal: p value < 2.2e-16, secretory-papillary: p value = 0.4435, ****: p value < 0.0001). e Left: UMAP plot depicting the correlation between iCAFs and myCAFs (as shown in a) and the four fibroblast subpopulations already present in healthy skin and identified in our original integrated scRNA-seq analysis (see Fig. 1). Right: Bar plot with the proportion of cutaneous iCAFs and myCAFs related to secretory-papillary, secretory-reticular, pro-inflammatory and mesenchymal fibroblasts. Statistical analyses of the differences were performed using two-sided paired t-tests (pro-inflammatory: p value = 0.0000111, secretory-reticular: p value = 0.00315, mesenchymal: p value = 0.000000955, secretory-papillary: p value = 0.109, **: p value < 0.01, ****: p value < 0.0001). iCAF: inflammatory cancer-associated fibroblast, myCAF myofibroblastic cancer-associated fibroblast, BD Bowen’s disease, cSCC cutaneous squamous cell carcinoma, n.s.: not significant. Source data are provided as a Source Data file.