A human embryonic stem cell reporter line for monitoring chemical-induced cardiotoxicity. Academic Article uri icon

Overview

abstract

  • AIMS: Human embryonic stem cells (hESCs) can be used to generate scalable numbers of cardiomyocytes (CMs) for studying cardiac biology, disease modelling, drug screens, and potentially for regenerative therapies. A fluorescence-based reporter line will significantly enhance our capacities to visualize the derivation, survival, and function of hESC-derived CMs. Our goal was to develop a reporter cell line for real-time monitoring of live hESC-derived CMs. METHODS AND RESULTS: We used CRISPR/Cas9 to knock a mCherry reporter gene into the MYH6 locus of hESC lines, H1 and H9, enabling real-time monitoring of the generation of CMs. MYH6:mCherry+ cells express atrial or ventricular markers and display a range of cardiomyocyte action potential morphologies. At 20 days of differentiation, MYH6:mCherry+ cells show features characteristic of human CMs and can be used successfully to monitor drug-induced cardiotoxicity and oleic acid-induced cardiac arrhythmia. CONCLUSION: We created two MYH6:mCherry hESC reporter lines and documented the application of these lines for disease modelling relevant to cardiomyocyte biology.

publication date

  • March 1, 2020

Research

keywords

  • Arrhythmias, Cardiac
  • Cell Differentiation
  • Doxorubicin
  • Heart Diseases
  • Human Embryonic Stem Cells
  • Myocytes, Cardiac
  • Oleic Acid

Identity

PubMed Central ID

  • PMC7252441

Scopus Document Identifier

  • 85081144974

Digital Object Identifier (DOI)

  • 10.1093/cvr/cvz148

PubMed ID

  • 31173076

Additional Document Info

volume

  • 116

issue

  • 3