TY - JOUR
T1 - Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming
AU - Folmes, Clifford D.L.
AU - Nelson, Timothy J.
AU - Martinez-Fernandez, Almudena
AU - Arrell, D. Kent
AU - Lindor, Jelena Zlatkovic
AU - Dzeja, Petras P.
AU - Ikeda, Yasuhiro
AU - Perez-Terzic, Carmen
AU - Terzic, Andre
N1 - Funding Information:
The authors thank Mayo Clinic Nuclear Magnetic Resonance Core and Flow Cytometry/Optical Morphology Shared Resource for assistance. This work was supported by the National Institutes of Health (R01HL083439, T32HL007111, R01HL085208, R56AI074363), Canadian Institutes of Health Research, Marriott Program, and Mayo Clinic.
PY - 2011/8/3
Y1 - 2011/8/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960945131&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960945131&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2011.06.011
DO - 10.1016/j.cmet.2011.06.011
M3 - Article
C2 - 21803296
AN - SCOPUS:79960945131
SN - 1550-4131
VL - 14
SP - 264
EP - 271
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -