Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform

verfasst von

Natalie Weber, Kathrin Kowalski, Tim Holler, Ante Radocaj, Martin Fischer, Stefan Thiemann, Jeanne de la Roche, Kristin Schwanke, Birgit Piep, Neele Peschel, Uwe Krumm, Alexander Lingk, Meike Wendland, Stephan Greten, Jan Dieter Schmitto, Issam Ismail, Gregor Warnecke, Urs Zywietz, Boris Chichkov, Joachim Meißner, Axel Haverich, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft

Abstract

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent an attractive model to investigate CM function and disease mechanisms. One characteristic marker of ventricular specificity of human CMs is expression of the ventricular, slow β-myosin heavy chain (MyHC), as opposed to the atrial, fast α-MyHC. The main aim of this study was to investigate at the single-cell level whether contraction kinetics and electrical activity of hESC-CMs are influenced by the relative expression of α-MyHC versus β-MyHC. For effective assignment of functional parameters to the expression of both MyHC isoforms at protein and mRNA levels in the very same hESC-CMs, we developed a single-cell mapping technique. Surprisingly, α- versus β-MyHC was not related to specific contractile or electrophysiological properties of the same cells. The multiparametric cell-by-cell analysis suggests that in hESC-CMs the expression of genes associated with electrical activity, contraction, calcium handling, and MyHCs is independently regulated.

Externe Organisation(en)

Medizinische Hochschule Hannover (MHH)
Laser Zentrum Hannover e.V. (LZH)

Typ

Artikel

Journal

Stem cell reports

Band

14

Seiten

788-802

Anzahl der Seiten

15

ISSN

2213-6711

Publikationsdatum

12.05.2020

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Biochemie, Genetik, Entwicklungsbiologie, Zellbiologie

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.stemcr.2020.03.015 (Zugang: Offen)