Extended Data Fig. 4: Transcriptome and metabolome profiles of senescent myoblasts.
A,D: Heat maps showing modules of temporally coexpressed (A) genes and (D) metabolites for myoblasts undergoing RAS-OIS using an unsupervised weighted clustering network analysis (WGCNA) approach. Roman numerals refer to different coexpression clusters. Data are expressed as row Z scores collected from (A) two and (D) three biologically independent experiments per condition. B: Functional over-representation map depicting Molecular Signaling Database(MSigDB) hallmark (H.) gene sets associated with each transcriptomic cluster for the indicated senescence inducers. 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 S2. C: Expression heat map of core senescence genes for myoblasts undergoing RAS-OIS. E: Fold change of the ratios between the indicated metabolites or of metabolite levels in myoblasts undergoing RAS-OIS (n = 3), measured at the indicated time point of the kinetics and relative to the values of proliferating cells. Data are presented as mean values +/- SD. Indicated p values were calculated using an unpaired two-sided Student’s t-test. F: Fold change of the ratios between the indicated metabolites or of metabolite levels in myoblasts undergoing replicative senescence (n = 6) and relative to the values of proliferating cells. Data are presented as mean values +/- SD. Indicated p values were calculated using an unpaired two-sided Student’s t-test. G-J: Fold changes kinetics of the indicated metabolites belonging to the SAMS in myoblasts undergoing RAS-OIS. n = 3 biologically independent experiments for each time point. Indicated p values were calculated using an unpaired two-sided Student’s t-test. Data are presented as mean values +/- SD. (The panel C contains small letters and numbers that overlap with the heatmap and the X axis. They need to be removed).
