Fig. 3: Surprisal analysis identifies MITF as a transcription factor regulating the bifurcation. | Nature Communications

Fig. 3: Surprisal analysis identifies MITF as a transcription factor regulating the bifurcation.

From: Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line

Fig. 3: Surprisal analysis identifies MITF as a transcription factor regulating the bifurcation.The alternative text for this image may have been generated using AI.

a Visualization of the influence score of the two regulatory modules identified from surprisal analysis. Module 1 is time-dependent, whereas module 2 exhibits a path-specific pattern. The dashed black lines indicate the region for which the respective module scores of each cell approach zero. b Pearson’s correlation between individual marker levels and the module 2 score. c, d Boxplot of Ki67 and MITF expression level in module 2 score-high and -low subpopulations at day 0. Data are median with first and third quartiles (box), and top and bottom quartiles (whiskers) indicated. Each experiment is the result of n = 16 biologically independent cells per group. e Ki67 relative expression, measured by qPCR in sorted MITF-High and MITF-Low cells at day 0. Each experiment is the result of n = 3 biologically independent samples per group. f Doubling time measured in treatment-naive condition, collected from sorted MITF-High and MITF-Low cells at day 0. Each experiment is the result of n = 3 biologically independent samples per group. g Single-cell time-lapsed microscopy analysis of MITF-activity during 5 days of BRAFi. Top panel: time-lapse images of sorted GFP-High and GFP-Low cells before and after 5 days of BRAFi. Representative images from three biological replicates are shown. Scale bar, 100 µm. Bottom panel: single-cell MITF-reporter traces for MITF-High (orange) and MITF-Low (blue) cells. Bold lines represent the mean response. h Slug, MITF, MART1, and PFK relative expression levels in module 2 score-high and -low subpopulations, collected from cells at day 5 and analyzed from the single-cell dataset. Each experiment is the result of n = 16 biologically independent samples per group. i Slug, MITF, Mart1, and PFK expression, measured by qPCR in sorted MITF-High and MITF-Low day-0 cells that have been treated with BRAFi for 5 days. Each experiment is the result of n = 3 biologically independent samples per group. Data are presented as mean values ± SEM. Source data are provided as a Source Data file.

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