title: Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells.
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.
authors.affiliation: Department of Vertebrate Genomics, Molecular Embryology and Aging Group, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prigione
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
mesh_terms: D000975:Antioxidants; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D046228:Microarray Analysis; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human