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01.07.2020 | Original Contribution

Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells

verfasst von: Mohamed M. Bekhite, Andrés González Delgado, Florian Menz, Tom Kretzschmar, Jasmine M. F. Wu, Tarek Bekfani, Sandor Nietzsche, Maria Wartenberg, Martin Westermann, Boris Greber, P. Christian Schulze

Erschienen in: Basic Research in Cardiology | Ausgabe 4/2020

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Abstract

Human-induced pluripotent stem cells (h-iPSCs) are a unique in vitro model for cardiovascular research. To realize the potential applications of h-iPSCs-derived cardiomyocytes (CMs) for drug testing or regenerative medicine and disease modeling, characterization of the metabolic features is critical. Here, we show the transcriptional profile during stages of cardiomyogenesis of h-iPSCs-derived CMs. CM differentiation was not only characterized by the expression of mature structural components (MLC2v, MYH7) but also accompanied by a significant increase in mature metabolic gene expression and activity. Our data revealed a distinct substrate switch from glucose to fatty acids utilization for ATP production. Basal respiration and respiratory capacity in 9 days h-iPSCs-derived CMs were glycolysis-dependent with a shift towards a more oxidative metabolic phenotype at 14 and 28 day old CMs. Furthermore, mitochondrial analysis characterized the early and mature forms of mitochondria during cardiomyogenesis. These results suggest that changes in cellular metabolic phenotype are accompanied by increased O₂ consumption and ATP synthesis to fulfill the metabolic needs of mature CMs activity. To further determine functionality, the physiological response of h-iPSCs-derived CMs to β-adrenergic stimulation was tested. These data provide a unique in vitro human heart model for the understanding of CM physiology and metabolic function which may provide useful insight into metabolic diseases as well as novel therapeutic options.

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Titel: Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells
verfasst von: Mohamed M. Bekhite
Andrés González Delgado
Florian Menz
Tom Kretzschmar
Jasmine M. F. Wu
Tarek Bekfani
Sandor Nietzsche
Maria Wartenberg
Martin Westermann
Boris Greber
P. Christian Schulze
Publikationsdatum: 01.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 4/2020
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-020-0796-0

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Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells

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