(a) Principal component analysis of AmpliSeq RNA-sequencing data in F5 and F5 + PPP3CC hiPSC-CMs showed cell line-specific responses with tacrolimus or rosiglitazone treatment. Over-expression of PPP3CC in F5 enabled phenotypic rescue; 7-day tacrolimus treatment had no deleterious effects in (b) contractility, (c, d) sarcomere organization, (e) ROS/RNS production, or (f) mitochondrial DNA (mtDNA) content in hiPSC-CMs. In addition, 7-day rosiglitazone treatment led to (e) significant decrease in ROS/RNS production and (f) enrichment in mitochondrial content, without any deleterious effects in (b) contractility or (c, d) sarcomere organization. Y-axis represents data normalized to the undertreated sample for the F5 + PPP3CC cell line. RQ; relative quantification; RU, relative units; BPM, beats per minute; BD75, 75% of beat duration; TCM, tacrolimus; RSG, rosiglitazone. See also Figure S7.