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  Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells.

Prigione, A., & Adjaye, J. (2010). Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells. International Journal of Developmental Biology, 54(11/12), 1729-1741. doi:10.1387/ijdb.103198ap.

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Genre: Journal Article
Alternative Title : Int J Dev Biol

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 Creators:
Prigione, A.1, 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              

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Free keywords: iPS cells; reprogramming; differentiation; mitochondria: metabolism
 Abstract: Reprogramming somatic cells to induced pluripotent stem (iPS) cells transforms differentiated cells to an embryonic stem (ES) cell-like state characterized by the acquisition of pluripotency and self-renewal capabilities. We recently demonstrated that human ES and iPS cells share similar mitochondrial properties and bioenergetic metabolism, which are distinct from those of fibroblasts. In the present study, we have applied a global transcriptome profiling approach to compare the mitochondrial-related transcriptional signature upon the loss of self renewal and pluripotency in human ES and iPS cells. This was achieved by inducing in vitro and in vivo spontaneous differentiation. ES and iPS cells showed a similar degree of correlation both in the undifferentiated state and in all the stages of differentiation analyzed, suggesting that their transcriptional similarities are retained upon differentiation. Moreover, comparable induction of transcripts involved in epithelial to mesenchymal transition was observed in both cell types. Analysis of mitochondrial-related nuclear transcripts revealed consensual regulation of genes involved in mitochondrial biogenesis and bioenergetic metabolism upon in vitro differentiation of human ES and iPS cells, while specific differences were identified within in vivo differentiated cells. Significant changes were not detected for antioxidant-related genes. Finally, we formulate a "metabolic state hypothesis" linking mitochondrial state and cellular metabolism to the stage of differentiation. Overall, our data unveil differences and similarities between human ES and iPS cells during spontaneous differentiation and suggest that the study of mitochondrial and metabolic remodeling may reveal key mechanisms underlying the acquisition, maintenance and exit of a self-renewing pluripotent state.

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Language(s): eng - English
 Dates: 2010
 Publication Status: Published in print
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Title: International Journal of Developmental Biology
  Alternative Title : Int J Dev Biol
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 54 (11/12) Sequence Number: - Start / End Page: 1729 - 1741 Identifier: ISSN: 0214-6282