Research Paper Advance Articles

Figure 3. ABT-263 induced changes in aged skin involving apoptosis and mitochondrial oxidative phosphorylation. (A) Volcano plot corresponding to a Wald test of RNA sequencing data obtained from aged skin treated with DMSO (n=4) or ABT-263 (n=3). Selected genes with significant and strong differential expression (FDR q < 0.05, |fold change| > 2, indicated by dashed lines) are colored according to their function. (B) Gene Set Enrichment Analysis (GSEA) enrichment plots demonstrating significant (FDR q < 0.05) coordinate up- and down-regulation, respectively, of apoptosis (Hallmark) and mitochondrial electron transport train (WikiPathways, WP295) in ABT-263- vs DMSO-treated aged skin. (C) Heatmap of Bcl2 and leading edge genes from each gene set that are also individually significant and strongly regulated by ABT-263 (Wald FDR q < 0.05, |fold change| > 2). Fold changes for downregulated genes are represented with their negative reciprocal (i.e., values of +2 and -2 correspond to two-fold up- or down-regulation by ABT-263, respectively). Genes are ordered alphanumerically by symbol within each gene set. Variance-stabilizing-transformed expression values are z-score-normalized to a mean of zero and SD of 1 across all samples in each column, with blue, white and red indicating z scores of ≤ 2, 0, and ≥ 2, respectively.