IP3R-Mediated Compensatory Mechanism for Calcium Handling in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Cardiac Ryanodine Receptor Deficiency.

ABSTRACT: In adult cardiomyocytes (CMs), the type 2 ryanodine receptor (RYR2) is an indispensable Ca²⁺ release channel that ensures the integrity of excitation-contraction coupling, which is fundamental for every heartbeat. However, the role and importance of RYR2 during human embryonic cardiac development are still poorly understood. Here, we generated two human induced pluripotent stem cell (iPSC)-based RYR2 knockout (RYR2^-/-) lines using the CRISPR/Cas9 gene editing technology. We found that RYR2^-/--iPSCs could differentiate into CMs with the efficiency similar to control-iPSCs (Ctrl-iPSCs); however, the survival of iPSC-CMs was markedly affected by the lack of functional RYR2. While Ctrl-iPSC-CMs exhibited regular Ca²⁺ handling, we observed sign

SUBMITTER: Luo X 

PROVIDER: S-EPMC7434870 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature