The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells§

Authors

  • Alessandro Prigione,

    1. Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
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  • Beatrix Fauler,

    1. Electron Microscopy Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
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  • Rudi Lurz,

    1. Electron Microscopy Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
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  • Hans Lehrach,

    1. Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
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  • James Adjaye

    Corresponding author
    1. Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany
    • Ihnestrasse 73, D-14195 Berlin, Germany

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    • Telephone: 0049-30-8413-1203; Fax: 0049-30-8413-1128


  • Author contributions: A.P.: conception and design, data collection and interpretation, manuscript writing; B.F. data collection; R.L. data interpretation; H.L infrastructure support; J.A. conception, data interpretation, manuscript writing.

  • First published online in STEM CELLS EXPRESS March 3, 2010.

  • §

    Disclosure of potential conflicts of interest is found at the end of this article.

Abstract

The ability of stem cells to propagate indefinitely is believed to occur via the fine modulation of pathways commonly involved in cellular senescence, including the telomerase, the p53, and the mitochondrial/oxidative stress pathways. Induced pluripotent stem cells (iPSCs) are a novel stem cell population obtained from somatic cells through forced expression of a set of genes normally expressed in embryonic stem cells (ESCs). These reprogrammed cells acquire self-renewal properties and appear almost undistinguishable from ESCs in terms of morphology, gene expression, and differentiation potential. Accordingly, iPSCs exhibit alterations of the senescence-related telomerase and p53 signaling pathways. However, although treatments with antioxidants have been recently shown to enhance cellular reprogramming, detailed information regarding the state of the mitochondrial/oxidative stress pathway in iPSCs is still lacking. Mitochondria undergo specific changes during organismal development and aging. Thus, addressing whether somatic mitochondria within iPSCs acquire ESC-like features or retain the phenotype of the parental cell is an unanswered but relevant question. Herein, we demonstrate that somatic mitochondria within human iPSCs revert to an immature ESC-like state with respect to organelle morphology and distribution, expression of nuclear factors involved in mitochondrial biogenesis, content of mitochondrial DNA, intracellular ATP level, oxidative damage, and lactate generation. Upon differentiation, mitochondria within iPSCs and ESCs exhibited analogous maturation and anaerobic-to-aerobic metabolic modifications. Overall, the data highlight that human iPSCs and ESCs, although not identical, share similar mitochondrial properties and suggest that cellular reprogramming can modulate the mitochondrial/oxidative stress pathway, thus inducing a rejuvenated state capable of escaping cellular senescence. STEM CELLS 2010;28:721–733

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