Extended Data Fig. 5: Rapamycin and DMOG revert transcriptomic features of senescence.

A: Heat map showing modules of temporally coexpressed genes for WI38 cells undergoing etoposide-mediated DDIS in the presence (+) or the absence (-) of rapamycin (Rapa) at the indicated time points using an unsupervised weighted clustering network analysis (WGCNA) approach. B: Functional over-representation map depicting Molecular Signaling Database (MSigDB) hallmark gene sets associated with each transcriptomic module (Fig. 3c) for cells undergoing etoposide-mediated DDIS in the presence or the absence of rapamycin. C: Heat map showing modules of temporally coexpressed genes for WI38 fibroblasts undergoing RAS-OIS and treated or not with DMOG at the indicated time points using an unsupervised weighted clustering network analysis (WGCNA) approach. For panels A, C, roman numerals refer to different modules. Data are expressed as row Z scores collected from two biologically independent experiments per condition. D: Functional over-representation map depicting Molecular Signaling Database (MSigDB) hallmark gene sets associated with each transcriptomic module (Fig. 3d) for cells undergoing RAS-OIS in the presence or the absence of DMOG. For panels B,D, circles are colour-coded according to the FDR-corrected p value based on the hypergeometric text comparing the overlap between the set of genes in each cluster and the respective list of genes in each MSigDB pathway. Size is proportional to the percentage of genes in the MsigDB gene set belonging to the cluster. N > 100 genes per transcriptomic module for each senescence inducer. Exact values for raw p values, adjusted p values and overlap (absolute and relative) between each pair of sets are reported in Supplementary Table S6 E: River plot depicting the overlaps between gene expression modules in cells undergoing RAS-OIS in the absence or presence of DMOG and cells undergoing DDIS in the absence or presence of rapamycin (Rapa). Blue and red tracks highlight genes down- and upregulated in both senescence perturbation experiments. F: Heat map showing modules of temporally coexpressed metabolites in WI38 fibroblasts undergoing etoposide-mediated DDIS in the presence or the absence of rapamycin for the indicated times using a hierarchical clustering approach. G: Heat map showing modules of temporally coexpressed metabolites for RAS-OIS cells in the presence (+) and absence (-) of DMOG at the indicated time points using a hierarchical clustering approach. For panels F, G, data are expressed as row Z scores collected from three biologically independent experiments per condition and time point.