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  The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells.

Prigione, A., Fauler, B., Lurz, R., Lehrach, H., & Adjaye, J. (2010). The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells, 28(4), 721-733. doi:10.1002/stem.404.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7BB1-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-CA99-B
Genre: Journal Article
Alternative Title : Stem Cells

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 Creators:
Prigione, A.1, Author              
Fauler, B.2, Author              
Lurz, R.2, Author              
Lehrach, H.3, Author              
Adjaye, J.1, Author              
Affiliations:
1Molecular Embryology and Aging (James Adjaye), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479654              
2Imaging/Electron Microscopy (Head: Rudi Lurz/Thorsten Mielke), Scientific Service (Head: Manuela B. Urban), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
3Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: iPS; Reprogramming; Aging; Gene expression; Differentiation; Embryonic stem cells; Induced pluripotency
 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.

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Language(s): eng - English
 Dates: 2010-03-03
 Publication Status: Published in print
 Pages: -
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 Rev. Method: -
 Identifiers: eDoc: 554597
DOI: 10.1002/stem.404
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Title: Stem Cells
  Alternative Title : Stem Cells
Source Genre: Journal
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Pages: - Volume / Issue: 28 (4) Sequence Number: - Start / End Page: 721 - 733 Identifier: ISSN: 1066-5099