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Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform.
Stem Cell Reports ( IF 5.9 ) Pub Date : 2020-04-16 , DOI: 10.1016/j.stemcr.2020.03.015
Natalie Weber 1 , Kathrin Kowalski 1 , Tim Holler 1 , Ante Radocaj 1 , Martin Fischer 2 , Stefan Thiemann 2 , Jeanne de la Roche 2 , Kristin Schwanke 3 , Birgit Piep 1 , Neele Peschel 1 , Uwe Krumm 1 , Alexander Lingk 1 , Meike Wendland 1 , Stephan Greten 1 , Jan Dieter Schmitto 3 , Issam Ismail 3 , Gregor Warnecke 3 , Urs Zywietz 4 , Boris Chichkov 4 , Joachim Meißner 1 , Axel Haverich 3 , Ulrich Martin 3 , Bernhard Brenner 1 , Robert Zweigerdt 3 , Theresia Kraft 1
Affiliation  

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.



中文翻译:

先进的单细胞定位揭示了hESC心肌细胞的收缩动力学和动作电位独立于肌球蛋白同工型。

人多能干细胞衍生的心肌细胞(hPSC-CMs)是研究CM功能和疾病机制的有吸引力的模型。人CM的心室特异性的一个特征性标志是心室慢β-肌球蛋白重链(MyHC)的表达,而不是心房快速α-MyHC。这项研究的主要目的是在单细胞水平上研究hESC-CMs的收缩动力学和电活动是否受α-MyHC与β-MyHC相对表达的影响。为了在相同的hESC-CM中有效分配功能参数,以同时在蛋白质和mRNA水平表达MyHC异构体,我们开发了一种单细胞作图技术。出乎意料的是,α-与β-MyHC与相同细胞的特异性收缩或电生理特性无关。

更新日期:2020-04-16
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