Fig. 6: The pro-mitotic effect of N-Cadherin/β-Catenin cascade is conserved in human iPSC-derived CMs (hiPSC-CMs).

a Knocking down CDH2 in human iPSC-derived CMs (hiPSC-CMs) led to a significant reduction in their proliferative activity as evidenced by decreased EdU labeling (N = 3 in each group, n = 24 for Scramble; and n = 26 for CDH2 KD hiPSC-CMs). A two-tailed t-test was utilized for comparison between groups. b Ectopic expression of CTNNB1 in hiPSC-CMs rescued the suppressed proliferative activity resulting from CDH2 depletion (N = 3 in each group, n = 22 for Scramble + Ctrl; n = 38 for CDH2 KD + Ctrl; and n = 23 for CDH2 KD + CTNNB1 OE hiPSC-CMs). Overexpression of WT CDH2, but not C-terminus-truncated CDH2 (ΔCDH2), increased the proliferative activity (N = 3 in each group, n = 46 for Ctrl; n = 72 for CDH2 OE; and n = 65 for ΔCDH2 OE hiPSC-CMs) (c) and nuclear accumulation of β-Catenin (d) in hiPSC-CMs (N = 3 in each group, n = 487 for Ctrl; n = 998 for CDH2 OE; and n = 751 for ΔCDH2 OE hiPSC-CMs). A one-way ANOVA test (p = 0.0014 in b; p = 0.013 in c; and p < 0.0001 in d) was utilized followed by a Tukey post-test correction. N-Cadherin and β-Catenin were highly co-localized at the cell membrane of hiPSC-CMs (n = 4). All experimental data are presented as means ± SEM. Exact p values are indicated in figures.