Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform
| Autor: | 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 |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene isoform Contraction (grammar) Human Embryonic Stem Cells Kinetics Action Potentials macromolecular substances Biology single-cell mapping technique Biochemistry Article 03 medical and health sciences MYH7 action potential 0302 clinical medicine human embryonic stem cell-derived cardiomyocytes MYH6 Myosin Genetics Humans Protein Isoforms Myocytes Cardiac Gene Cells Cultured health care economics and organizations Myosin Heavy Chains maturation Cell Differentiation Cell Biology musculoskeletal system Myocardial Contraction Cell biology twitch contractions Electrophysiology cardiac myosin heavy chain 030104 developmental biology Single-Cell Analysis Cardiac Myosins tissues 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary 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. Highlights • Single-cell mapping technique allows multiparametric characterization of hESC-CMs • Twitch and action potential kinetics are independent of MyHC isoform in hESC-CMs • Myosin-mRNA levels are only weakly correlated with respective protein levels In this article, Natalie Weber and colleagues developed a single-cell mapping technique for multiparametric analysis of hESC cardiomyocytes (hESC-CMs). Characterization of function (twitch and action potential) in direct relation to the expressed myosin heavy chain isoform by multiparametric analysis suggests that in hESC-CMs the expression of genes associated with electrical activity, contraction, calcium handling, and myosin heavy chains is independently regulated. |
| Databáze: | OpenAIRE |
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