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dc.contributor.authorEmanuelli, Giulia
dc.contributor.authorZoccarato, Anna
dc.contributor.authorReumiller, Christina M
dc.contributor.authorPapadopoulos, Angelos
dc.contributor.authorChong, Mei
dc.contributor.authorRebs, Sabine
dc.contributor.authorBetteridge, Kai
dc.contributor.authorBeretta, Matteo
dc.contributor.authorStreckfuss-Bömeke, Katrin
dc.contributor.authorShah, Ajay M
dc.date.accessioned2022-01-25T00:30:19Z
dc.date.available2022-01-25T00:30:19Z
dc.date.issued2022-03
dc.identifier.issn0022-2828
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332893
dc.description.abstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are an increasingly employed model in cardiac research and drug discovery. As cellular metabolism plays an integral role in determining phenotype, the characterization of the metabolic profile of hiPSC-CM during maturation is crucial for their translational application. In this study we employ a combination of methods including extracellular flux, 13C-glucose enrichment and targeted metabolomics to characterize the metabolic profile of hiPSC-CM during their maturation in culture from 6 weeks, up to 12 weeks. Results show a progressive remodeling of pathways involved in energy metabolism and substrate utilization along with an increase in sarcomere regularity. The oxidative capacity of hiPSC-CM and particularly their ability to utilize fatty acids increased with time. In parallel, relative glucose oxidation was reduced while glutamine oxidation was maintained at similar levels. There was also evidence of increased coupling of glycolysis to mitochondrial respiration, and away from glycolytic branch pathways at later stages of maturation. The rate of glycolysis as assessed by lactate production was maintained at both stages but with significant alterations in proximal glycolytic enzymes such as hexokinase and phosphofructokinase. We observed a progressive maturation of mitochondrial oxidative capacity at comparable levels of mitochondrial content between these time-points with enhancement of mitochondrial network structure. These results show that the metabolic profile of hiPSC-CM is progressively restructured, recapitulating aspects of early post-natal heart development. This would be particularly important to consider when employing these cell model in studies where metabolism plays an important role.
dc.format.mediumPrint-Electronic
dc.publisherElsevier BV
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectCardiac cell models
dc.subjectEnergy metabolism
dc.subjectMetabolic maturation
dc.subjectMetabolic shift
dc.subjectiPSC-derived cardiomyocytes
dc.titleA roadmap for the characterization of energy metabolism in human cardiomyocytes derived from induced pluripotent stem cells.
dc.typeArticle
dc.publisher.departmentC.I.M.R. Medicine
dc.date.updated2022-01-04T08:47:55Z
prism.endingPage147
prism.publicationDate2021
prism.publicationNameJ Mol Cell Cardiol
prism.startingPage136
prism.volume164
dc.identifier.doi10.17863/CAM.80323
dcterms.dateAccepted2021-12-01
rioxxterms.versionofrecord10.1016/j.yjmcc.2021.12.001
rioxxterms.versionAM
dc.contributor.orcidEmanuelli, Giulia [0000-0001-8899-6110]
dc.identifier.eissn1095-8584
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-12-17
cam.orpheus.success2022-01-24 - Embargo set during processing via Fast-track
cam.depositDate2022-01-04
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-12-16


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