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

1,2,3email, 4,5,6email, 4,6email, 4,7email, 1,6email, 2,8email, 1,9email, 10email, 11email, 2,12email, 2,7email, 13email, 10email, 4,* email and 2,14,* email
Received: 5 August 2011; in revised form: 25 October 2011 / Accepted: 4 November 2011 / Published: 7 November 2011
(This article belongs to the Section Molecular Diagnostics)
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.
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
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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2011; 12(11):7554-7568.

Chicago/Turabian Style

Huang, Pin-I; Chou, Yueh-Ching; Chang, Yuh-Lih; Chien, Yueh; Chen, Kuan-Hsuan; Song, Wen-Shin; Peng, Chi-Hsien; Chang, Chin-Hong; Lee, Shin-Da; Lu, Kai-Hsi; Chen, Yi-Jen; Kuo, Chia-Hua; Hsu, Chuan-Chih; Lee, Hsin-Chen; Yung, Ming-Chi. 2011. "Enhanced Differentiation of Three-Gene-Reprogrammed Induced Pluripotent Stem Cells into Adipocytes via Adenoviral-Mediated PGC-1α Overexpression." Int. J. Mol. Sci. 12, no. 11: 7554-7568.

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