摘要
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 over expression in 3-gene iPSCs. PGC-1α over expression 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 over expression 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 over expression 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.
原文 | 英語 |
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頁(從 - 到) | 7554-7568 |
頁數 | 15 |
期刊 | International Journal of Molecular Sciences |
卷 | 12 |
發行號 | 11 |
DOIs | |
出版狀態 | 已發佈 - 十一月 2011 |
對外發佈 | Yes |
ASJC Scopus subject areas
- Computer Science Applications
- Molecular Biology
- Catalysis
- Inorganic Chemistry
- Spectroscopy
- Organic Chemistry
- Physical and Theoretical Chemistry
- Medicine(all)