| Autor: |
Pardon, Gaspard, Vander Roest, Alison S., Chirikian, Orlando, Birnbaum, Foster, Lewis, Henry, Castillo, Erica A., Wilson, Robin, Denisin, Aleksandra K., Blair, Cheavar A., Holbrook, Colin, Koleckar, Kassie, Chang, Alex C. Y., Blau, Helen M., Pruitt, Beth L. |
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| Zdroj: |
Nature Communications; 6/26/2024, Vol. 15 Issue 1, p1-19, 19p |
| Abstrakt: |
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/− drug treatment; +/− cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies. Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models. Here the authors report CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time at increased throughput. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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