TY - JOUR
T1 - Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells
AU - Folmes, Clifford D.L.
AU - Martinez-Fernandez, Almudena
AU - Faustino, Randolph S.
AU - Yamada, Satsuki
AU - Perez-Terzic, Carmen
AU - Nelson, Timothy J.
AU - Terzic, Andre
N1 - Funding Information:
Acknowledgments This work was supported by the National Institutes of Health, Canadian Institutes of Health Research, American Heart Association, Fondation Leducq, Marriott Foundation, and Mayo Clinic Center for Regenerative Medicine.
PY - 2013/2
Y1 - 2013/2
N2 - Reprogramming strategies influence the differentiation capacity of derived induced pluripotent stem (iPS) cells. Removal of the reprogramming factor c-Myc reduces tumorigenic incidence and increases cardiogenic potential of iPS cells. c-Myc is a regulator of energy metabolism, yet the impact on metabolic reprogramming underlying pluripotent induction is unknown. Here, mitochondrial and metabolic interrogation of iPS cells derived with (4F) and without (3F) c-Myc demonstrated that nuclear reprogramming consistently reverted mitochondria to embryonic-like immature structures. Metabolomic profiling segregated derived iPS cells from the parental somatic source based on the attained pluripotency-associated glycolytic phenotype and discriminated between 3F versus 4F clones based upon glycolytic intermediates. Real-time flux analysis demonstrated a greater glycolytic capacity in 4F iPS cells, in the setting of equivalent oxidative capacity to 3F iPS cells. Thus, inclusion of c-Myc potentiates the pluripotent glycolytic behavior of derived iPS cells, supporting c-Myc-free reprogramming as a strategy to facilitate oxidative metabolism-dependent lineage engagement.
AB - Reprogramming strategies influence the differentiation capacity of derived induced pluripotent stem (iPS) cells. Removal of the reprogramming factor c-Myc reduces tumorigenic incidence and increases cardiogenic potential of iPS cells. c-Myc is a regulator of energy metabolism, yet the impact on metabolic reprogramming underlying pluripotent induction is unknown. Here, mitochondrial and metabolic interrogation of iPS cells derived with (4F) and without (3F) c-Myc demonstrated that nuclear reprogramming consistently reverted mitochondria to embryonic-like immature structures. Metabolomic profiling segregated derived iPS cells from the parental somatic source based on the attained pluripotency-associated glycolytic phenotype and discriminated between 3F versus 4F clones based upon glycolytic intermediates. Real-time flux analysis demonstrated a greater glycolytic capacity in 4F iPS cells, in the setting of equivalent oxidative capacity to 3F iPS cells. Thus, inclusion of c-Myc potentiates the pluripotent glycolytic behavior of derived iPS cells, supporting c-Myc-free reprogramming as a strategy to facilitate oxidative metabolism-dependent lineage engagement.
KW - Cardiac differentiation
KW - Cardiogenesis
KW - Glycolysis
KW - Metabolomics
KW - Mitochondria
KW - Oxidative phosphorylation
KW - Stem cell metabolism
KW - iPS cells
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U2 - 10.1007/s12265-012-9431-2
DO - 10.1007/s12265-012-9431-2
M3 - Article
C2 - 23247633
AN - SCOPUS:84872613340
SN - 1937-5387
VL - 6
SP - 10
EP - 21
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
IS - 1
ER -