Electrophysiological Properties of Tetraploid Cardiomyocytes Derived from Murine Pluripotent Stem Cells Generated by Fusion of Adult Somatic Cells with Embryonic Stem Cells

Author:

Xu Guoxing12ORCID,Fatima Azra1,Breitbach Martin3,Kuzmenkin Alexey1,Fügemann Christopher J.3,Ivanyuk Dina1,Kim Kee Pyo4,Cantz Tobias4ORCID,Pfannkuche Kurt1ORCID,Schöler Hans R.4,Fleischmann Bernd K.3ORCID,Hescheler Jürgen1,Šarić Tomo1ORCID

Affiliation:

1. Center for Physiology and Pathophysiology, Institute for Neurophysiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany

2. Department of Physiology and Chinese-German Stem Cell Center, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

3. Institute of Physiology I, Life & Brain Center, Medical Faculty, University of Bonn, 53115 Bonn, Germany

4. Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, 48149 Münster, Germany

Abstract

Most cardiomyocytes (CMs) in the adult mammalian heart are either binucleated or contain a single polyploid nucleus. Recent studies have shown that polyploidy in CMs plays an important role as an adaptive response to physiological demands and environmental stress and correlates with poor cardiac regenerative ability after injury. However, knowledge about the functional properties of polyploid CMs is limited. In this study, we generated tetraploid pluripotent stem cells (PSCs) by fusion of murine embryonic stem cells (ESCs) and somatic cells isolated from bone marrow or spleen and performed a comparative analysis of the electrophysiological properties of tetraploid fusion-derived PSCs and diploid ESC-derived CMs. Fusion-derived PSCs exhibited characteristics of genuine ESCs and contained a near-tetraploid genome. Ploidy features and marker expression were also retained during the differentiation of fusion-derived cells. Fusion-derived PSCs gave rise to CMs, which were similar to their diploid ESC counterparts in terms of their expression of typical cardiospecific markers, sarcomeric organization, action potential parameters, response to pharmacologic stimulation with various drugs, and expression of functional ion channels. These results suggest that the state of ploidy does not significantly affect the structural and electrophysiological properties of murine PSC-derived CMs. These results extend our knowledge of the functional properties of polyploid CMs and contribute to a better understanding of their biological role in the adult heart.

Funder

Federal Ministry for Education and Research

Moritz Stiftung and Köln-Fortune Program

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference98 articles.

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