Figure 8.

Schematic representation of loss of Dp427 consequences in hiPSC-CMs. Consequences of the altered genotype (loss of Dp427) on phenotypic adaptions include structural-functional alterations in DMD-hiPSC-CMs (orange/yellow-green panel respectively). Deficit of caveoloe formation may slow down Ca²⁺ transients and maintain more dependence to sarcolemmal Ca²⁺ entry. On the other side, impaired maturation of specific sarcomere determinants may result in weaker myofibril tension production. Increased Ca²⁺-sensitivity of tension development and cellular hypertrophy may potentially rescue cell contractility at low load. Slower Ca²⁺ transient kinetics and myofibril relaxation are likely a main cause of slower cell contractility. Dashed lines refer to hypothetic mechanisms to explore. Colourful progress bars (Days 0 to 100 from cardiac differentiation) refer to findings of this work and previous studies on these DMD-hiPSC-CM lines.^13,15