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Abstract #4407

Metabolic Changes of Human Embryonic Stem Cells During Cardiomyocyte Differentiation

Anna V. Naumova1, Daciana H. Margineantu2, Kareen L. Kreutziger3, Nathan J. Palpant3, James Fugate3, Charles E. Murry3

1Radiology, University of Washington, Seattle, WA, United States; 2Fred Hutchinson Cancer Research Center, Seattle, WA, United States; 3Department of Pathology, University of Washington, Seattle, WA, United States

Despite the literature data demonstrating that anaerobic glycolytic metabolism sufficient for mouse embryonic stem cell homeostasis, we demonstrated that undifferentiated human embryonic stem cells have active mitochondrial metabolism reflected by a high respiratory rate. Our data also demonstrate greater metabolic flexibility of differentiated cardiomyocytes characterized by a quick shift of ATP production from respiration to glycolysis in conditions where mitochondrial ATP production is impaired. Measurement of respiration and glycolysis rates by extracellular flux analysis using Seahorse analyzer and assessment of high energy phosphates by 31P NMR spectroscopy are complementary to each other for evaluation of metabolic activity on live cells.

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Keywords

acidification active adult anaerobic analyzer assessment basal beating biochemical block blue broadening cancer capacity cause cell cells chemical competent complementary compounds conditioned conditions consumption content conversion culture death decreased degree delivery depletion derivatives derived despite differentiated differentiation directed embryonic energetically energetics energy evaluated evaluation expected extracellular failure findings flexibility flux fold folds form function generate generated glucose graft greater growth heart help homeostasis human impaired induce induced inhibition initiation injection inorganic insufficient integrals largest live made mainly maintained marked maximal measured measuring media membrane metabolic metabolically metabolism month mouse nature normalized nutrients opposite optimize orange oxidative oxygen oxygenated pathology pathway pathways peak phosphate phosphates placed positive potential preliminary previous produced production promising protocol quick radiology reach reflected reflecting repair represented represents reserve resolution respiration respiratory response restore science seahorse significantly since spectrometer spectroscopy spectrum stem stress studies sufficient supplemented sweep synthesis synthesized temperature therapeutic transplantation transplanted trends uncoupling understanding undifferentiated width