Proteomics

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Contractile work contributes to maturation of energy metabolism in hiPSC-derived cardiomyocytes


ABSTRACT: Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for biomedical application, but they are immature and have not undergone metabolic shift related to early postnatal development. Cultivation of hiPSC-CM in 3D engineered heart tissue (EHT) format leads to morphological maturation. This study compared the mitochondrial and metabolic state of hiPSC-CM in standard 2D culture and the EHT format and determined the influence of contractile activity. HiPSC-CM in EHTs showed ~2-fold higher number of mitochondria (electron microscopy), mitochondrial mass (mitotracker), DNA (Mt-ND1, Mt-ND2), and protein abundance (proteome) than in 2D culture. While hiPSC-CM exhibited the principal ability to use glucose, lactate and fatty acids as energy substrates irrespective of culture format, hiPSC-CM in 3D performed more oxidation of glucose, lactate and fatty acid, and less anaerobic glycolysis. The increase in mitochondrial mass and DNA in 3D was diminished by pharmacological inhibition of contractile force, suggesting that contractile work participates in mitochondrial development hiPSC-CM. In conclusion, contractile work in the EHT format contributes to metabolic maturation of hiPSC-CM.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

SUBMITTER: Andrea Stoehr  

LAB HEAD: Arne Hansen

PROVIDER: PXD008205 | Pride | 2018-03-06

REPOSITORIES: Pride

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Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes.

Ulmer Bärbel M BM   Stoehr Andrea A   Schulze Mirja L ML   Patel Sajni S   Gucek Marjan M   Mannhardt Ingra I   Funcke Sandra S   Murphy Elizabeth E   Eschenhagen Thomas T   Hansen Arne A  

Stem cell reports 20180301 3


Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising tool for biomedical application, but they are immature and have not undergone metabolic maturation related to early postnatal development. To assess whether cultivation of hiPSC-CMs in 3D engineered heart tissue format leads to maturation of energy metabolism, we analyzed the mitochondrial and metabolic state of 3D hiPSC-CMs and compared it with 2D cu  ...[more]

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