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

J Cardiovasc Transl Res. 2013 Feb;6(1):10-21. doi: 10.1007/s12265-012-9431-2. Epub 2012 Dec 18.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Cellular Reprogramming*
  • Gene Expression Regulation
  • Glycolysis* / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Metabolomics / methods
  • Mice
  • Mitochondria / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Oxidation-Reduction
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Time Factors
  • Transfection

Substances

  • Biomarkers
  • Proto-Oncogene Proteins c-myc