Figure 7: Gene expression changes induced by Tert expression in the heart.
(a) Summary table indicating that various gene sets are differentially regulated in the comparisons MI versus sham and Tert (MI) versus empty (MI). The corresponding affected biological pathways are indicated. (b) GSEA plots for the indicated pathways in heart tissue. Microarray genes were ranked based on the two-tailed t-statistic tests obtained from the AAV9-Tert versus AAV9-empty by pair-wise comparisons. The red to blue horizontal bar represents the ranked list. Those genes showing higher expression levels for each cohort are located at the edges of the bar (I=infarct+AAV9-empty; IT infarct+AAV9-Tert). The genes located at the central area of the bar show small differences in gene expression fold changes between both groups. A heatmap of indicated core-enriched genes is displayed on the right of each enrichment plot. (c) Relative mRNA expression level (qRT–PCR) of Fgfr3, Bmpr1b, Irf7 and Itgb6 in AAV9-empty versus AAV9-Tert confirm candidate genes found among the most differentially expressed genes in GSEA represented as fold change relative to AAV9-empty group. n, number of mice. Mean values with s.e.m are represented. Statistical analysis: two-sided Student’s t-test, P-values are shown. (d) GSEA analysis reveals a regenerative signature in Tert-treated mice. The represented gene sets were generated using the expression profiles in neonatal mice (day1=D1) described by Haubner et al.7 Selections for up- and downregulated genes were based on FDR values <0.01 in their comparison of gene expression profiles between D1 and D10. For GSEA Kolmogorov–Smirnoff testing was used for statistical analysis. The FDR is calculated by Benjamini and Hochberg FDR correction.
