hERG-deficient human embryonic stem cell-derived cardiomyocytes for modelling QT prolongation.

Stem Cell Research & Therapy
Yun ChangFeng Lan

Abstract

Long-QT syndrome type 2 (LQT2) is a common malignant hereditary arrhythmia. Due to the lack of suitable animal and human models, the pathogenesis of LQT2 caused by human ether-a-go-go-related gene (hERG) deficiency is still unclear. In this study, we generated an hERG-deficient human cardiomyocyte (CM) model that simulates 'human homozygous hERG mutations' to explore the underlying impact of hERG dysfunction and the genotype-phenotype relationship of hERG deficiency. The KCNH2 was knocked out in the human embryonic stem cell (hESC) H9 line using the CRISPR/Cas9 system. Using a chemically defined differentiation protocol, we obtained and verified hERG-deficient CMs. Subsequently, high-throughput microelectrode array (MEA) assays and drug interventions were performed to characterise the electrophysiological signatures of hERG-deficient cell lines. Our results showed that KCNH2 knockout did not affect the pluripotency or differentiation efficiency of H9 cells. Using high-throughput MEA assays, we found that the electric field potential duration and action potential duration of hERG-deficient CMs were significantly longer than those of normal CMs. The hERG-deficient lines also exhibited irregular rhythm and some early afterdepolari...Continue Reading

References

Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·J W Warmke, B Ganetzky
Aug 22, 2001·American Journal of Physiology. Heart and Circulatory Physiology·M BrunnerG Koren
Jan 24, 2002·Nature·Eduardo Marbán
Dec 5, 2003·Trends in Pharmacological Sciences·Luiz BelardinelliMarc A Vos
Oct 7, 2004·Journal of the American College of Nutrition·Kenji HoshinoYoshikatsu Eto
Jul 26, 2006·Expert Opinion on Drug Metabolism & Toxicology·Phillip J StansfeldJohn S Mitcheson
Oct 14, 2006·The Journal of Physiology·Guy Salama, Barry London
Jan 17, 2008·Pflügers Archiv : European journal of physiology·Gong Xin LiuGideon Koren
Feb 16, 2010·Journal of Pharmacological and Toxicological Methods·Shengde PengAndrew Bruening-Wright
Jan 18, 2011·Nature·Ilanit ItzhakiLior Gepstein
Sep 3, 2013·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Silvia G PrioriUNKNOWN Asia Pacific Heart Rhythm Society
Jun 16, 2014·Nature Methods·Paul W BurridgeJoseph C Wu
Aug 2, 2014·Journal of the American College of Cardiology·Yongming WangJoseph C Wu
Nov 25, 2014·Nature Communications·Corey L AndersonCraig T January
Jul 16, 2015·Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie·Simon W Rabkin
Sep 30, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Mari Ohnuki, Kazutoshi Takahashi
Nov 26, 2015·Best Practice & Research. Clinical Obstetrics & Gynaecology·Pauliina DamdimopoulouOuti Hovatta
Nov 4, 2016·Physiological Reviews·M S BohnenR S Kass
Nov 4, 2016·The Journal of Physiology·Nipavan ChiamvimonvatJeanne M Nerbonne
Aug 28, 2017·Current Opinion in Genetics & Development·Daniel Ortmann, Ludovic Vallier
Mar 25, 2018·Microscopy Research and Technique·Gong ChengChaofeng Sun
Mar 27, 2018·Chinese Medical Journal·Feng WangJian-Yan Wen
Jun 30, 2018·Journal of the American College of Cardiology·Priyanka GargJoseph C Wu

❮ Previous
Next ❯

Software Mentioned

AxIS Navigator
Cardiac Analysis Tool
Origin
AxIS export tool

Related Concepts

Related Feeds

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.