Journal: Frontiers in Epigenetics and Epigenomics
Article Title: Transcription factor network dynamics during the commitment to oncogene-induced senescence
doi: 10.3389/freae.2024.1423454
Figure Lengend Snippet: FIGURE 1 Transcriptional landscape of WI38 fibroblasts during the first 24 h of oncogenic HRASG12V overexpression. (A) Diagram describing the experimental approach for the time-resolved multi-omic profiling used to define the early gene-regulatory networks preceding OIS commitment. (B) Euler diagrams showing overlaps of differentially expressed genes (DEGs) for each time point in the time series relative to proliferating cells (0 h). (C) PCA projection plots showing the individual transcriptional trajectories of DEGs identified within 24 h of RAS induction. Two biologically independent time series are shown. (D) Heatmap showing the number-coded modules (I-IV) of DEGs identified within 24 h of RAS overexpression. Two biologically independent time series experiments are shown. (E) Functional over-representation analysis map showing significant associations of the Molecular Signatures Database (MSigDB) Hallmark gene sets for each module described in (D). Circle fill is color-coded according to the FDR-corrected p-value from a hypergeometric distribution test. Circle size is proportional to the percentage of genes in each MSigDB gene set found within each gene module. N > 200 genes per module. (F) PCA projection plots showing the trajectories of DEGs identified through the entire time series (up to 144 h after RAS overexpression). (G) (Continued)
Article Snippet: WI38 normal human lung fibroblasts (CCL-75, ATCC -American Type Culture Collection) and GM21808 normal human skin fibroblasts (Coriell Institute) were cultured in a DMEM (D6429, Millipore-Sigma) medium supplemented with 10% fetal bovine serum, (#25–514, GenClone) at 37°C in a 5% CO2 and 2% O2 atmosphere.
Techniques: Over Expression, Functional Assay