title: Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.
abstract: The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, stemness factor-mediated nuclear reprogramming reverted mitochondrial networks into cristae-poor structures. Metabolomic footprinting and fingerprinting distinguished derived pluripotent progeny from parental fibroblasts according to elevated glucose utilization and production of glycolytic end products. Temporal sampling demonstrated glycolytic gene potentiation prior to induction of pluripotent markers. Functional metamorphosis of somatic oxidative phosphorylation into acquired pluripotent glycolytic metabolism conformed to an embryonic-like archetype. Stimulation of glycolysis promoted, while blockade of glycolytic enzyme activity blunted, reprogramming efficiency. Metaboproteomics resolved upregulated glycolytic enzymes and downregulated electron transport chain complex I subunits underlying cell fate determination. Thus, the energetic infrastructure of somatic cells transitions into a required glycolytic metabotype to fuel induction of pluripotency.
authors.affiliation: Center for Regenerative Medicine and Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Clifford D L
authors.initials: CD
authors.lastname: Folmes
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
authors.forename: Almudena
authors.initials: A
authors.lastname: Martinez-Fernandez
authors.forename: D Kent
authors.initials: DK
authors.lastname: Arrell
authors.forename: Jelena Zlatkovic
authors.initials: JZ
authors.lastname: Lindor
authors.forename: Petras P
authors.initials: PP
authors.lastname: Dzeja
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Carmen
authors.initials: C
authors.lastname: Perez-Terzic
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D065150:Cellular Reprogramming; D004579:Electron Transport; D004734:Energy Metabolism; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D055432:Metabolomics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D039904:Pluripotent Stem Cells / Q000378:metabolism*
chemical_list: D005947:Glucose