Fig. 4: scRNA-seq reveals upregulation of ATF4 stress signalling in escapees. | Nature Communications

Fig. 4: scRNA-seq reveals upregulation of ATF4 stress signalling in escapees.

From: Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signalling

Fig. 4: scRNA-seq reveals upregulation of ATF4 stress signalling in escapees.The alternative text for this image may have been generated using AI.

a Co-visualization of untreated (bottom left) and treated (top right) scRNA-seq datasets on a single t-SNE plot, showing escapees in orange and non-escapees in blue (see Supplementary Fig. 3d for classification of escapee and non-escapee). Untreated proliferative cells (UT-P) and quiescent cells (UT-Q) were coloured grey and green, respectively. Escapees can be identified as a small orange peninsula in the treated condition. b Venn diagram of differentially expressed genes as described in the text. Genes labelled with a green star are ATF4 target genes. c MSigDB hallmark gene set enrichment analysis of the 40 genes using the false-discovery rate cutoff of 0.05. d Violin plot showing ATF4 protein levels by immunofluorescence in four melanoma cell lines treated with 1-µM dabrafenib for 72 h. Split violin shows ATF4 levels in non-escapees (NE) and escapees (E) identified by phospho-Rb (S780) co-staining. Each population value is pooled from three replicate wells. e The percentage of pRb+ cells in the indicated conditions. Cells were treated for 72 h. Error bars: mean ± std of four replicate wells, representative of two experimental repeats. f Percentage of late-apoptotic A375 cells with or without ATF4 knockdown, after a 96-h treatment with the indicated drugs. Error bars: mean ± std of three biological replicates, representative of two experimental repeats. Source data are provided as a Source Data file.

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