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

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...

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Bibliographic Details
Published in:Basic research in cardiology 2020-07, Vol.115 (4), p.37-37, Article 37
Main Authors: Bekhite, Mohamed M., González Delgado, Andrés, Menz, Florian, Kretzschmar, Tom, Wu, Jasmine M. F., Bekfani, Tarek, Nietzsche, Sandor, Wartenberg, Maria, Westermann, Martin, Greber, Boris, Schulze, P. Christian
Format: Article
Language:English
Subjects:
ATP
Cardiology
Cardiomyocytes
Fatty acids
Gene expression
Glycolysis
Human influences
Medicine
Medicine & Public Health
Metabolic disorders
Metabolism
Mitochondria
Original Contribution
Oxygen consumption
Phenotypes
Pluripotency
Regenerative medicine
Stem cells
Substrates
Transcription
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Summary: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 O 2 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.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-020-0796-0