real-time-measurements-calcium-contractility-parameters-human-induced

Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful tool for studying mutation-mediated changes in cardiomyocyte ...

association-serum-lncrna-casc11-with-injury-severity-inflammation

Association of Serum lncRNA <em>CASC11</em> with Injury Severity and Inflammation in Spinal Cord Injury

Spinal cord injury (SCI) is a severe central nervous system trauma. This single-center, observational and in vitro study investigated the diagnostic ...

Vanderbilt School of Medicine

The First Affiliated Hospital of Naval Medical University

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising tool for disease modeling and drug development. However, hiPSC-CMs remain functionally immature, which hinders their utility as a model of human cardiomyocytes.

Triiodothyronine and dexamethasone alter potassium channel expression and promote electrophysiological maturation of human-induced pluripotent stem cell-derived cardiomyocytes.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder with patients typically showing heterozygous inheritance of a pathogenic variant in a gene encoding a contractile protein. Here, we study the contractile effects of a rare homozygous mutation using explanted tissue and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to gain insight into how the balance between mutant and WT protein expression affects cardiomyocyte function.

Low expression of the K280N  mutation is sufficient to increase basal myofilament activation in human hypertrophy cardiomyopathy.

Triadin knockout syndrome (TKOS) is a malignant arrhythmia disorder caused by recessive null variants in TRDN-encoded cardiac triadin. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from two unrelated TKOS patients and an unrelated control. CRISPR-Cas9 gene editing was used to insert homozygous TRDN-p.D18fs13 into a control line to generate a TKOS model (TRDN). Western blot confirmed total knockout of triadin in patient-specific and TRDN iPSC-CMs. iPSC-CMs from both patients revealed a prolonged action potential duration (APD) at 90% repolarization, and this was normalized by protein replacement of triadin. APD prolongation was confirmed in TRDN iPSC-CMs. TRDN iPSC-CMs revealed that loss of triadin underlies decreased expression and co-localization of key calcium handling proteins, slow and decreased calcium release from the sarcoplasmic reticulum, and slow inactivation of the L-type calcium channel leading to frequent cellular arrhythmias, including early and delayed afterdepolarizations and APD alternans.

ArticleTotal : 2	Year
Publication title Cited by 7	2023
Publication title	2026

Article	Year
Triiodothyronine and dexamethasone alter potassium channel expression and promote electrophysiological maturation of human-induced pluripotent stem cell-derived cardiomyocytes. Journal of molecular and cellular cardiology\| PubMed ID: 34400182	2021
Low expression of the K280N mutation is sufficient to increase basal myofilament activation in human hypertrophy cardiomyopathy. Journal of molecular and cellular cardiology plus\| PubMed ID: 37159677	2022
Cellular and electrophysiological characterization of triadin knockout syndrome using induced pluripotent stem cell-derived cardiomyocytes. Stem cell reports\| PubMed ID: 37163978	2023

Lili Wang

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