Fig. 1

Dynamic transcriptome changes in HDF induced by vemurafenib. Stimulation was done with 2 µM of vemurafenib (PLX4032) or analog volume of vehicle (DMSO) for the indicated duration. A Principal component analysis of the transcriptomics datasets in HDF. The eigenvalues from the first two main components (PC1-PC2) are plotted, and the percentage of variance explained by each one is indicated in brackets. Average changes in the expression states are suggested by the dashed trajectories. B UpSet plot showing the number of differentially expressed genes (DEG; q < 0.05) in HDF stimulated with vemurafenib in comparison to DMSO control. C Significantly over-represented (q < 0.1) biological processes among the genes up-regulated by vemurafenib treatment. Every node represents a single GO term colored by stimulation time, with the node size indicating the number of up-regulated genes within each term. Nodes are connected based on their similarity score (combined Jaccard + Overlap score > 0.4). D Soft clustering based on the top 30% of genes with the highest fold changes. The number of genes within every cluster is indicated in brackets; only genes with a minimum membership score of 0.6 are included. Significantly over-represented (q < 0.05) biological processes for every cluster are shown in the adjacent bar plot. E Flow cytometry-based determination of the proliferative state. Top: quantification (mean ± SEM) of the percentage of proliferative cells (Ki67 positive) for three independent experiments (n = 3). Bottom: representative histograms showing the frequency distribution of Ki67 levels for the indicated conditions