Fig. 2

Melphalan treatment of hiPSC-CMs results in Ca²⁺ handling defect and alters expression of genes encoding calcium channels and sarcomeric proteins. a Representative traces showing intracellular Ca²⁺ transients in hiPSC-CMs treated with melphalan for 3 days. i, normal Ca²⁺ transients; ii–vi, abnormal Ca²⁺ transients. b Stacked bar charts showing percentage of CMs exhibiting normal (blue) or abnormal Ca²⁺ transients (red) under each condition. Sample sizes (n) were denoted at the top of each bar. c Quantification of peak amplitude, transient duration, maximum upstroke speed, and maximum decay speed of Ca²⁺ transients under each condition. Relative values were calculated based on the average values of the melphalan-treated group vs. untreated group (n = 22). d qRT-PCR panel showing relative gene expression levels of Ca²⁺ transporting-related genes including RYR2 and CACNA1C, and CM structure-related genes including TNNI1, TNNT2, MYH6/7, and MYL2/7 in hiPSC-CMs treated with melphalan for 3 days (n = 3). Relative expression values were calculated based on the average values of the melphalan-treated group vs. untreated group. Comparisons were conducted between each treatment group and no melphalan group via two-sided chi-square test for b or one-way ANOVA test for c and d. *P value < 0.05; **P value < 0.01; ***P value < 0.001; ****P value < 0.0001