Supplementary Figure 3: Activation of NOTCH is associated with cell-cycle arrest and antagonism of the RAS-driven secretome.
From: NOTCH1 mediates a switch between two distinct secretomes during senescence
(a) Multiple cell-cycle-related genesets were significantly enriched within downregulated genes from IMR90 cells with N1ICD- (NIS), HRASG12V-(RIS), or Etoposide-induced senescence (DDIS). Upper: example Geneset enrichment analysis (GSEA) plots for the ‘Reactome–cell cycle’ geneset in the indicated senescence dataset (NES, normalised enrichment score; FDR, false discovery rate); lower: table demonstrating enrichment of multiple cell-cycle genesets in down-regulated genes. (b) GSEA demonstrating enrichment of publically available TGF-β1-signatures in transcriptomic data from IMR90 cells stably expressing N1ICD (NIS). (c) Differentially expressed transcripts in cells expressing N1ICD-, HRASG12V-or both (NIS, RIS, or N+RIS, respectively), compared to normal control cells. Heat map shows z-score normalised fold changes of 1150 secretome genes differentially expressed in at least in one comparison. Representative KEGG pathways enriched in five clusters (FDR < 0.01) are shown. Note, GLB1 encodes the lysosomal enzyme responsible for SA-β-Gal activity.
