Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells

Clifford Folmes, Almudena Martinez-Fernandez, Randolph S. Faustino, Satsuki Yamada, Carmen M Terzic, Timothy J Nelson, Andre Terzic

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34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10-21
Number of pages12
JournalJournal of Cardiovascular Translational Research
Volume6
Issue number1
DOIs
StatePublished - Feb 2013

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Induced Pluripotent Stem Cells
Metabolomics
Cellular Reprogramming
Energy Metabolism
Mitochondria
Clone Cells
Phenotype
Incidence

Keywords

  • Cardiac differentiation
  • Cardiogenesis
  • Glycolysis
  • iPS cells
  • Metabolomics
  • Mitochondria
  • Oxidative phosphorylation
  • Stem cell metabolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics
  • Genetics(clinical)
  • Molecular Medicine
  • Pharmaceutical Science

Cite this

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abstract = "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.",
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AU - Martinez-Fernandez, Almudena

AU - Faustino, Randolph S.

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AU - Terzic, Carmen M

AU - Nelson, Timothy J

AU - Terzic, Andre

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