Mutation-Specific Phenotypes in hiPSC-Derived Cardiomyocytes Carrying Either Myosin-Binding Protein C Or α-Tropomyosin Mutation for Hypertrophic Cardiomyopathy

Figure 2

The cell size and Ca²⁺ handling of hiPSC-derived CMs after 1-, 3-, and 6-week culture as single cells. (a) Representative images of WT-CMs (WT), HCMT-CMs (HCMT), and HCMM-CMs (HCMM) stained with antibodies for cTnT (red) and MYBPC (green) proteins. Scale bars are 100 μm. (b) The size of the HCMM-CMs was significantly larger in all three time points when compared to WT- and HCMT-CMs ( when compared to WT-CMs or HCMT-CMs in the 1-week time point, when compared to WT-CMs or HCMT-CMs in 3-week time point, and when compared to WT-CMs or HCMT-CMs in 6-week time point). HCMT-CMs were significantly larger than WT-CMs in 3-week time point ( when compared to WT-CMs. , except in HCMT 6 w .) (c) The proportion of the multinucleated CMs was significantly higher in HCMT-CMs than in WT-CMs and HCMM-CMs when both cell lines and all time points were combined for each group (in statistical analysis , ). The averages of multinucleated CMs were determined from the same cells, whose sizes and numbers are presented in (b). (d) Significantly more CMs with Ca²⁺ handling abnormalities were observed in HCMT-CMs than in WT-CMs and HCMM-CMs when both cell lines and all time points were combined for each group (in statistical analysis , ). The proportions of CMs with abnormalities in their Ca²⁺ handling were determined from the same Ca²⁺ imaging results presented in (f). The total numbers of the analyzed CMs are presented in (f). (e) Representative images of Ca²⁺ rhythm categories. (f) Distributions of hiPSC-derived CMs in different Ca²⁺ rhythm categories (e) in each time point. WT1 = UTA.04602.WT, WT2 = UTA.04511.WT, HCMT1 = UTA.02912.HCMT, HCMT2 = UTA.13602.HCMT, HCMM1 = UTA.07801.HCMM, and HCMM2 = UTA.06108.HCMM.

(a)

(b)

(c)

(d)

(e)

(f)