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Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
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School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
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Cancer center, Taipei Veterans General Hospital, Taipei 112, Taiwan
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Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan
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College of Pharmacology, Taipei Medical University, Taipei 110, Taiwan
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Department of Pharmacy, Taipei Veterans General Hospital, Taipei 112, Taiwan
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Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
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Department of Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan
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Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan
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Department of Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan
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Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 404, Taiwan
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Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei 112, Taiwan
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Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 111, Taiwan
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Divison of Cardiovascular Surgery, Department of Surgery, Taiwan Adventist Hospital, Taipei 105, Taiwan
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Abstract
Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown
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Induced pluripotent stem cells formed by the introduction of only three factors, Oct4/Sox2/Klf4 (3-gene iPSCs), may provide a safer option for stem cell-based therapy than iPSCs conventionally introduced with four-gene iPSCs. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays an important role during brown fat development. However, the potential roles of PGC-1α in regulating mitochondrial biogenesis and the differentiation of iPSCs are still unclear. Here, we investigated the effects of adenovirus-mediated PGC-1α overexpression in 3-gene iPSCs. PGC-1α overexpression resulted in increased mitochondrial mass, reactive oxygen species production, and oxygen consumption. Microarray-based bioinformatics showed that the gene expression pattern of PGC-1α-overexpressing 3-gene iPSCs resembled the expression pattern observed in adipocytes. Furthermore, PGC-1α overexpression enhanced adipogenic differentiation and the expression of several brown fat markers, including uncoupling protein-1, cytochrome C, and nuclear respiratory factor-1, whereas it inhibited the expression of the white fat marker uncoupling protein-2. Furthermore, PGC-1α overexpression significantly suppressed osteogenic differentiation. These data demonstrate that PGC-1α directs the differentiation of 3-gene iPSCs into adipocyte-like cells with features of brown fat cells. This may provide a therapeutic strategy for the treatment of mitochondrial disorders and obesity.
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