Na_V1.5 knockout in iPSCs: a novel approach to study Na_V1.5 variants in a human cardiomyocyte environment.

ABSTRACT: Cardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSC-CMs) successfully reproduce the mechanisms of several channelopathies. However, this approach involve cell reprogramming from somatic tissue biopsies or genomic editing in healthy iPSCs for every mutation found and to be investigated. We aim to knockout (KO) Na_V1.5, the cardiac sodium channel, in a healthy human iPSC line, characterize the model and then, use it to express variants of Na_V1.5. We develop a homozygous Na_V1.5 KO iPSC line able to differentiate into cardiomyocytes with CRISPR/Cas9 tool. The Na_V1.5 KO iPSC-CMs exhibited an organized contractile apparatus, spontaneous contractile activity, and electrophysiological recordings confirmed the major reduction

SUBMITTER: Pierre M 

PROVIDER: S-EPMC8387439 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature