Figure 5.

The pseudokinase TRIB3 contributes to the beneficial effects of PPi. (A) Gene set enrichment analysis enrichment plot for mammalian target of rapamycin signalling pathway in TNNT2^HOM induced pluripotent stem cell-cardiomyocytes. (B) Contractility analysis of TNNT2^HOM induced pluripotent stem cell-cardiomyocytes were treated with PPi in the presence of mammalian target of rapamycin inhibitors everolimus and rapamycin; n = 8–16 replicates from three independent differentiation batches. Box-and-whisker plots show the minimum, the 25th percentile, the median, the 75th percentile, and the maximum. (C) Relative contractility of siRNA control- or siTRIB3-transfected TNNT2^HET induced pluripotent stem cell-cardiomyocytes treated with PPi or vehicle control (Ctrl). n = 9–12 replicates from three independent differentiation batches. Box-and-whisker plots show the minimum, the 25th percentile, the median, the 75th percentile, and the maximum. (D) Relative mRNA expression of ATF4, PHGDH, and TRIB3 in siRNA control, siTRIB3- or siATF4- transfected TNNT2^HET induced pluripotent stem cell-cardiomyocytes treated with PPi or vehicle control (Ctrl). Mean ± standard deviation, n = 6–12.