Figure 6.

Paired-like homeodomain 2 levels are increased in mutant cardiomyocytes and repress expression of DSP, CX43, and NaV1.5

(A–D) Molecular analyses on 1-month-old Pa. DSP^{p.Tyr1188His/WT}, KI. DSP^{p.Tyr1188His/WT}, and isogenic control cardiomyocytes.

(A) Gene expression levels for PITX2 normalized to GUS.

(B and C) Representative immunoblots for PITX2 in Pa. DSP^{p.Tyr1188His/WT} (B) and KI. DSP^{p.Tyr1188His/WT} (C) cardiomyocytes.

(D) Quantification of PITX2 protein levels normalized to VIN.

(E–G) Molecular and functional analyses on 1-month-old control hiPSC-derived cardiomyocytes treated with either empty viral particles or particles encoding for PITX2 (lenti-PITX2).

(E) Representative immunoblots for PITX2, DSP, CX43, and NaV1.5. (F) Protein levels of PITX2, DSP, CX43, and NaV1.5 normalized to VIN.

(G) APD measured at 50% and 90% (control, n = 66 cell clusters; lenti-PITX2, n = 64 cell clusters) of cardiomyocyte repolarization.

Data are plotted as mean. The dots in (A), (D), (F), and (G) represent technical replicates, whereas the color of each dot indicates the experimental origin (3 independent experiments; 4–29 technical replicates). Significance has been assessed by a two-tailed unpaired Student’s t test or two-tailed Mann-Whitney test when data were not normally distributed (^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001, ns, not significant). KI, knockin; Pa., patient.