4.2 Article

Generation of homozygous Nav1.8 knock-out iPSC lines by CRISPR Cas9 genome editing to investigate a potential new antiarrhythmic strategy

Journal

STEM CELL RESEARCH
Volume 60, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.scr.2022.102677

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Funding

  1. Else-Kroner-Fresenius Stiftung
  2. Deutsche Forschungsgemeinschaft (DFG) through the International Research Training Group Award [(IRTG) 1816, IRTG 1816]

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In this study, induced pluripotent stem cells (iPSCs) with a homozygous SCN10A knockout were generated using CRISPR Cas9 genome editing. The edited iPSCs retained their pluripotency and differentiation capacity, allowing for the investigation of the role of Na(v)1.8 in the heart.
The sodium channel Na(v)1.8, encoded by SCN10A, is reported to contribute to arrhythmogenesis by inducing the late INa and thereby enhanced persistent Na+ current. However, its exact electrophysiological role in cardiomyocytes remains unclear. Here, we generated induced pluripotent stem cells (iPSCs) with a homozygous SCN10A knock-out from a healthy iPSC line by CRISPR Cas9 genome editing. The edited iPSCs maintained full pluripotency, genomic integrity, and spontaneous in vitro differentiation capacity. The iPSCs are able to differentiate into iPSC-cardiomyocytes, hence making it possible to investigate the role of Na(v)1.8 in the heart.

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