Details
| Original language | English |
|---|---|
| Pages (from-to) | 788-802 |
| Number of pages | 15 |
| Journal | Stem cell reports |
| Volume | 14 |
| Issue number | 5 |
| Early online date | 16 Apr 2020 |
| Publication status | Published - 12 May 2020 |
| Externally published | Yes |
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.
Keywords
- action potential, cardiac myosin heavy chain, human embryonic stem cell-derived cardiomyocytes, maturation, MYH6, MYH7, single-cell mapping technique, twitch contractions
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Genetics
- Biochemistry, Genetics and Molecular Biology(all)
- Developmental Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Stem cell reports, Vol. 14, No. 5, 12.05.2020, p. 788-802.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Advanced Single-Cell Mapping Reveals that in hESC Cardiomyocytes Contraction Kinetics and Action Potential Are Independent of Myosin Isoform
AU - Weber, Natalie
AU - Kowalski, Kathrin
AU - Holler, Tim
AU - Radocaj, Ante
AU - Fischer, Martin
AU - Thiemann, Stefan
AU - de la Roche, Jeanne
AU - Schwanke, Kristin
AU - Piep, Birgit
AU - Peschel, Neele
AU - Krumm, Uwe
AU - Lingk, Alexander
AU - Wendland, Meike
AU - Greten, Stephan
AU - Schmitto, Jan Dieter
AU - Ismail, Issam
AU - Warnecke, Gregor
AU - Zywietz, Urs
AU - Chichkov, Boris
AU - Meißner, Joachim
AU - Haverich, Axel
AU - Martin, Ulrich
AU - Brenner, Bernhard
AU - Zweigerdt, Robert
AU - Kraft, Theresia
N1 - Funding Information: This work was supported by grants from Deutsche Forschungsgemeinschaft ( DFG : BR849/31-1 , KR1187/21–1 , MA2331/16-1 , ZW64/4-1 and the Cluster of Excellence REBIRTH DFG EXC62/2 , EXC62/3 ; and KFO311 ZW64/7-1 ). R.Z. received funding from the German Ministry for Education and Science (grants: 13N14086 , 01EK1601A , 01EK1602A ), the European Union H2020 program (TECHNOBEAT, grant 66724 ), and StemBANCC (Innovative Medicines Initiative joint undertaking, grant agreement no. 115439-2, resources of which are composed of financial contribution from the European Union [ FP7/2007-2013 ] and EFPIA companies' in kind contribution). The authors have no disclosures.
PY - 2020/5/12
Y1 - 2020/5/12
N2 - 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.
AB - 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.
KW - action potential
KW - cardiac myosin heavy chain
KW - human embryonic stem cell-derived cardiomyocytes
KW - maturation
KW - MYH6
KW - MYH7
KW - single-cell mapping technique
KW - twitch contractions
UR - http://www.scopus.com/inward/record.url?scp=85084695137&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2020.03.015
DO - 10.1016/j.stemcr.2020.03.015
M3 - Article
C2 - 32302556
AN - SCOPUS:85084695137
VL - 14
SP - 788
EP - 802
JO - Stem cell reports
JF - Stem cell reports
SN - 2213-6711
IS - 5
ER -