Deep Phenotyping of Human Induced Pluripotent Stem Cell-derived Atrial and Ventricular Cardiomyocytes

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2018 Jun 22

PMID 29925689

Citations 135

Authors

Lukas Cyganek

Malte Tiburcy

Karolina Sekeres

Kathleen Gerstenberg

Hanibal Bohnenberger

Christof Lenz

Sarah Henze

Michael Stauske

Gabriela Salinas

Wolfram-Hubertus Zimmermann

Gerd Hasenfuss

Kaomei Guan

Affiliations

Soon will be listed here.

Abstract

Generation of homogeneous populations of subtype-specific cardiomyocytes (CMs) derived from human induced pluripotent stem cells (iPSCs) and their comprehensive phenotyping is crucial for a better understanding of the subtype-related disease mechanisms and as tools for the development of chamber-specific drugs. The goals of this study were to apply a simple and efficient method for differentiation of iPSCs into defined functional CM subtypes in feeder-free conditions and to obtain a comprehensive understanding of the molecular, cell biological, and functional properties of atrial and ventricular iPSC-CMs on both the single-cell and engineered heart muscle (EHM) level. By a stage-specific activation of retinoic acid signaling in monolayer-based and well-defined culture, we showed that cardiac progenitors can be directed towards a highly homogeneous population of atrial CMs. By combining the transcriptome and proteome profiling of the iPSC-CM subtypes with functional characterizations via optical action potential and calcium imaging, and with contractile analyses in EHM, we demonstrated that atrial and ventricular iPSC-CMs and -EHM highly correspond to the atrial and ventricular heart muscle, respectively. This study provides a comprehensive understanding of the molecular and functional identities characteristic of atrial and ventricular iPSC-CMs and -EHM and supports their suitability in disease modeling and chamber-specific drug screening.

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