Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming
By C. Folmes, Timothy J. Nelson, A. Martinez-Fernandez, D. K. Arrell, Jelena Zlatkovic Lindor, P. Dzeja, Y. Ikeda, C. Perez-Terzic, Andre Terzic. Cell Metabolism, 2011
960 citations recorded by the source corpus.
SUMMARY 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/8b91daf85df040c0388eeea376b5a5c723a8ad07
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In Molecular Biology
- Andre Terzic
- Fred H. Gage
- J. Gonçalves
- Eran Meshorer
- Timothy J. Nelson
- P. Dzeja
- Simon T. Schafer
- C. Folmes
Citations in the corpus
- Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, positive): “Stem cells seem to be in a metabolic state that is different from their progeny (Folmes et al., 2011; Varum et al., 2011).”
- Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, positive): “Genuine iPSCs demonstrate targeted upregulation of glycolytic enzymes and selective downregulation of electron transport chain subunits, associated with regression in mitochondrial density, distribution, and ultrastructure (Folmes et al., 2011a; Prigione et al., 2010; Varum et al., 2011).”
- Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. (2015, background): “These results suggest an underlying metabolic difference between cancer cells and PSCs, but also stand in contrast to the findings of Folmes and colleagues (Folmes et al., 2011).”