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Int. J. Mol. Sci. 2011, 12(11), 7554-7568; doi:10.3390/ijms12117554
Article

Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression

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1 Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan 2 School of Medicine, National Yang-Ming University, Taipei 112, Taiwan 3 Cancer center, Taipei Veterans General Hospital, Taipei 112, Taiwan 4 Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan 5 College of Pharmacology, Taipei Medical University, Taipei 110, Taiwan 6 Department of Pharmacy, Taipei Veterans General Hospital, Taipei 112, Taiwan 7 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan 8 Department of Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan 9 Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan 10 Department of Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan 11 Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 404, Taiwan 12 Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei 112, Taiwan 13 Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 111, Taiwan 14 Divison of Cardiovascular Surgery, Department of Surgery, Taiwan Adventist Hospital, Taipei 105, Taiwan
* Authors to whom correspondence should be addressed.
Received: 5 August 2011 / Revised: 25 October 2011 / Accepted: 4 November 2011 / Published: 7 November 2011
(This article belongs to the Section Molecular Pathology)
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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 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.
Keywords: induced pluripotent stem cell; c-Myc; peroxisome proliferator-activated receptor gamma coactivator-1α; brown adipocyte induced pluripotent stem cell; c-Myc; peroxisome proliferator-activated receptor gamma coactivator-1α; brown adipocyte
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Huang, P.-I.; Chou, Y.-C.; Chang, Y.-L.; Chien, Y.; Chen, K.-H.; Song, W.-S.; Peng, C.-H.; Chang, C.-H.; Lee, S.-D.; Lu, K.-H.; Chen, Y.-J.; Kuo, C.-H.; Hsu, C.-C.; Lee, H.-C.; Yung, M.-C. Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression. Int. J. Mol. Sci. 2011, 12, 7554-7568.

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