期刊
CELL METABOLISM
卷 14, 期 2, 页码 264-271出版社
CELL PRESS
DOI: 10.1016/j.cmet.2011.06.011
关键词
-
资金
- National Institutes of Health [R01HL083439, T32HL007111, R01HL085208, R56A1074363]
- Canadian Institutes of Health Research
- Marriott Program
- Mayo Clinic
The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, sternness factor-mediated nuclear reprogramming reverted mitochondria! 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.
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