Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.

ABSTRACT: Disease modeling using human induced pluripotent stem cells (hiPSCs) from patients with genetic disease is a powerful approach for dissecting pathophysiology and drug discovery. Nevertheless, isogenic controls are required to precisely compare phenotypic outcomes from presumed causative mutations rather than differences in genetic backgrounds. Moreover, 2D cellular models often fail to exhibit authentic disease phenotypes resulting in poor validation in vitro. Here we show that a combination of precision gene editing and bioengineered 3D tissue models can establish advanced isogenic hiPSC-derived cardiac disease models, overcoming these drawbacks. To model inherited cardiac arrhythmias we selected representative N588D and N588K missense mutations affecting the same codon in the hERG potass

SUBMITTER: Maurissen TL 

PROVIDER: S-EPMC10831092 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature