ArticleStem cell research & therapy2022
KCNQ1-deficient and KCNQ1-mutant human embryonic stem cell-derived cardiomyocytes for modeling QT prolongation.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 7 citations in OpenAlex.
- Bifidobacterium adolescentis attenuates cardiac remodeling in HFD/STZ-induced obesity-associated diabetic cardiomyopathy.Scientific reports · 2026Article
- Facing ethical concerns in the age of precise gene therapy: Outlook on inherited arrhythmias.World journal of cardiology · 2024Article
- Genome Editing and Cardiac Arrhythmias.Cells · 2023Review
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10 authors at 4 institutions in 1 country.
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Abstract
backgroundThe slowly activated delayed rectifier potassium current (I
methodKCNQ1 was knocked out in human embryonic stem cell (hESC) H9 line using the CRISPR/cas9 system. KCNQ1-deficient and KCNQ1-mutant hESCs were differentiated into CMs through a chemically defined differentiation protocol. Subsequently, high-throughput MEA analysis and drug intervention were performed to determine the electrophysiological characteristics of KCNQ1-deficient and KCNQ1-mutant CMs.
resultsDuring high-throughput MEA analysis, the electric field potential and action potential durations in KCNQ1-deficient CMs were significantly longer than those in wild-type CMs. KCNQ1-deficient CMs also showed an irregular rhythm. Furthermore, KCNQ1-deficient and KCNQ1-mutant CMs showed different responses to different drug treatments, which reflected the differences in their pathogenic mechanisms.
conclusionWe established a human CM model with KCNQ1 deficiency showing a prolonged QT interval and an irregular heart rhythm. Further, we used various drugs to treat KCNQ1-deficient and KCNQ1-mutant CMs, and the three models showed different responses to these drugs. These models can be used as important tools for studying the different pathogenic mechanisms of KCNQ1 mutation and the relationship between the genotype and phenotype of KCNQ1, thereby facilitating drug development.
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