(A-B) In the scatter plots, values on the abscissa are gene expression fold-change data from microarray data of Pawlikowski et al., 2013, comparing gene expression in cultured BrafV600E-transduced human melanocytes with mock-transduced human melanocytes. Log-transformed fold-change data from probe sets mapping to the same gene were averaged, and genes without clear mouse orthologs were discarded. Values on the ordinate are from the present study, comparing gene expression in nevus melanocyte from BrafV600E-expressing skin (Mel 0 and 1) with non-nevus melanocytes of either Mel 2 (panel A, putative melanocyte stem cells) or Mel 3 (panel B, hair follicle melanocytes) from wild-type skin. Each dot represents a single gene; in the right-hand plot of panel B, only genes that were found to be significantly different (adjusted p-value<0.05) between nevus melanocytes and Mel 3 melanocytes are shown. Points at the very bottom or top of each plot represent genes that showed no detectable expression in either the nevus melanocytes, or the non-nevus melanocytes, respectively. Lines of best fit are shown, along with the coefficient of determination (R2). The small positive correlation in B is largely driven by points in the lower left quadrant. The shaded area in the right panel of B highlights 99 jointly-statistically significant genes that are substantially affected in this quadrant. (C) Sixteen of the genes associated with the shaded area in the right-hand panel of B are associated with cell proliferation (meta-PCNA signature; see Figure 3), while 19 are Mitf-target genes (as described by Hoek et al., 2008; Rambow et al., 2015; Tirosh et al., 2016). The remaining 64 are listed here. (D–G) All plots are based on the left-hand plot in panel B, colored to highlight particular sets of genes. Panel D shows genes belonging to the meta-PCNA signature; the data imply that nevus cells and cultured BRAF-transformed melanocytes are both growth-inhibited. Panel E highlights Mitf (green) and Mitf-target genes (red). The data imply that Mitf and its targets are nearly all downregulated in BRAFV600E-transduced cultured melanocytes, but not in nevus melanocytes (compared with hair follicle melanocytes); instead, Mitf expression is little-changed, and only a subset of Mitf target genes is downregulated (these include melanin synthesis and melanosome biogenesis genes Gpr143, Mlana, Pmel, Slc45a2, Tyr and Tyrp1). Panel F highlights genes ‘universally’ associated with senescence (Hernandez-Segura et al., 2017; see Figure 3). The data show that the senescent phenotype of the cultured BRAFV600E-melanocytes is well captured by this signature, whereas the phenotype of nevus melanocytes is not. Panel G highlights those genes considered by Pawlikowski et al., 2013 to be SASP-associated, most of which are upregulated in BRAFV600E-transduced cultured melanocytes. A subset of these appears upregulated in nevus melanocytes (arrows), although the very high fold-change values of those genes marked by arrows simply reflect the fact that transcripts for these genes were not detected in hair follicle melanocytes.