Figure 4.

Doxorubicin Uptake, Calcium Handling, and Contractility

(A) Doxorubicin uptake in hiPSC-CMs with knockouts of SLC and ABC transporters (isotype, n = 11; SLC28A3-KO, n = 4; SLC22A17-KO, n = 6; SLC28A1-KO, n = 4; ABCC2-KO, n = 4; ABCB4-KO, n = 7; ABCC5-KO, n = 4; ABCC9-KO, n = 4; and ABCC10-KO, n = 4). n = full independent experimental replicates. (B) Effect of knocking out MYH7 and CELF4 on calcium transients. Left: representative calcium transients. Middle left: full width at half maximum (FWHM). Middle right: calcium transient duration 75% (CTD₇₅). Right: decay time. (C) Contractility analysis using impedance measurement in RIN3-KO, ZFN521-KO, and CYP2J2-KO hiPSC-CMs (ISO, n = 41; RIN3-KO, n = 48; ZFN521-KO, n = 48; and CYP2J2-KO, n = 89). n = number of assessed wells of 96-well plate derived from at least 3 independent rounds of differentiation (B and C). Error bars represent ±SEM. ∗P < 0.05, ∗∗P ≤ 0.01, ∗∗∗P < 0.001, and ∗∗∗∗P < 0.0001 by 2-way analysis of variance (A) and 1-way analysis of variance (B and C). Abbreviations as in Figure 2.