Generation of induced pluripotent stem cell lines from patients with LQT1 caused by heterozygous mutations in the KCNQ1 gene

Lu Ren; James W S Jahng; Nadjet Belbachir; Zachary Cook; Gabriela C Rivero; Marco V Perez; Joseph C Wu

doi:10.1016/j.scr.2024.103443

Generation of induced pluripotent stem cell lines from patients with LQT1 caused by heterozygous mutations in the KCNQ1 gene

Stem Cell Res. 2024 May 16:78:103443. doi: 10.1016/j.scr.2024.103443. Online ahead of print.

Authors

Lu Ren¹, James W S Jahng¹, Nadjet Belbachir¹, Zachary Cook², Gabriela C Rivero¹, Marco V Perez¹, Joseph C Wu³

Affiliations

¹ Stanford Cardiovascular Institute, Stanford, CA 94305, USA; Depart of Medicine, Division of Cardiovascular Medicine, Stanford, CA 94305, USA.
² Greenstone Biosciences, Palo Alto, CA 94304, USA.
³ Stanford Cardiovascular Institute, Stanford, CA 94305, USA; Depart of Medicine, Division of Cardiovascular Medicine, Stanford, CA 94305, USA. Electronic address: joewu@stanford.edu.

PMID: 38763038
DOI: 10.1016/j.scr.2024.103443

Abstract

Long QT Syndrome (LQTS) is a genetic heart disorder that can induce cardiac arrhythmias. The most prevalent subtype, LQT1, stems from rare variants in the KCNQ1 gene. Utilizing induced pluripotent stem cells (iPSCs) enables detailed cellular studies and personalized medicine approaches for this life-threatening condition. We generated two LQT1 iPSC lines with single nucleotide nonsense mutations, c.1031 C > T and c.1121 T > A in KCNQ1. Both lines exhibited typical iPSC morphology, expressed high levels of pluripotent markers, maintained normal karyotype, and possessed the capability to differentiate into three germ layers. These cell lines serve as important tools for investigating the biological mechanisms underlying LQT1 due to mutations in the KCNQ1 gene.

Keywords: Human induced pluripotent stem cell (iPSC); KCNQ1; Long QT Syndrome (LQTS).