Fig. 6

Fig. 6 Mitochondrial respiration and transcriptome analysis of iPSCs with homozygous TOM7 variant. (a) Volcano plot showing RNAseq results of upregulated and downregulated genes in TOMM7PL/PL when compared with WT cells. Genes in indicated pathways with adjusted P value < 0.05 and log2 (fold change) > 1 were in color. (b) Gene set enrichment analysis (GSEA) showing significantly upregulated Hallmark datasets and downregulated GO biological process terms in TOMM7PL/PL iPSCs when compared with WT cells. (c) Heatmap showing expression of differentially expressed genes (identified by comparing TOMM7PL/PL iPSCs with WT cells) in all genotypes. (d) Category network plot showing the linkage of significantly upregulated Hallmark gene sets in TOMM7PL/PL iPSCs when compared with WT cells. (e) Quantitative RT-PCR confirmed the differentially expressed genes in iPSCs. Statistical analysis was performed using Friedman test followed by Dunn's post hoc test, with comparisons made to WT cells. (f) Quantitative RT-PCR confirmed the differentially expressed genes in iEndo cells. Statistical analysis was performed using Friedman test followed by Dunn's post hoc test, with comparisons made to WT cells. (g) Immunoblotting in whole-cell lysate from iPSCs with anti-HK2 antibody. (h) Glycolysis in iPSCs measured by glycolytic proton efflux rate (PER) in Seahorse assay. Statistical analysis was performed using Mann–Whitney U-tests. WT, wild-type; Het, heterozygous TOMM7+/PL; Homo, homozygous TOMM7PL/PL; KO, TOMM7 knock-out TOMM7−/−. Data were presented as mean ± S.E.M. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.