Nuclear Reprogramming with c-Myc Potentiates Glycolytic Capacity of Derived Induced Pluripotent Stem Cells

  • Clifford D. L. Folmes
  • Almudena Martinez-Fernandez
  • Randolph S. Faustino
  • Satsuki Yamada
  • Carmen Perez-Terzic
  • Timothy J. Nelson
  • Andre Terzic
Article

DOI: 10.1007/s12265-012-9431-2

Cite this article as:
Folmes, C.D.L., Martinez-Fernandez, A., Faustino, R.S. et al. J. of Cardiovasc. Trans. Res. (2013) 6: 10. doi:10.1007/s12265-012-9431-2

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.

Keywords

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

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Clifford D. L. Folmes
    • 1
  • Almudena Martinez-Fernandez
    • 1
  • Randolph S. Faustino
    • 1
  • Satsuki Yamada
    • 1
  • Carmen Perez-Terzic
    • 1
  • Timothy J. Nelson
    • 1
  • Andre Terzic
    • 1
    • 2
  1. 1.Center for Regenerative Medicine and Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Departments of Medicine, Molecular Pharmacology & Experimental Therapeutics, and Medical GeneticsMayo ClinicRochesterUSA
  2. 2.Mayo ClinicRochesterUSA