Contractile characterization, metabolic flux, and cell size analysis of TNNT2:p.R286H iPSC-CMs (induced pluripotent stem cells derived cardiomyocytes).
A, Comparison of the percentage sarcomere shortening and (B) relaxation duration for isogenic wild type (WT), TNNT2:p.R286H (R286H/+) and established (+) hypertrophic variant of MYH7:p.R403Q (R403Q/+) iPSC-CMs. C, Measurement of oxygen consumption rate (OCR) and (D) extracellular acidification rate (ECAR) in WT, R286H/+ and R403Q/+ cardiomyocytes using the Seahorse platform and (E) unconstrained cell size in WT (n=586 cells), R286H/+ (n=408 cells) and (+) R403Q/+ (n=488 cells). All iPSC-CMs were generated by mutating an isogenic line, denoted TTN-GFP PGP1.21,22 Two or more differentiations were studied from 2 independent clones for each genotype. Data, mean ± SEM. Student t test for each mutant compared with WT was used where a significance cutoff of P<0.05 was used.