Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression

Pin I. Huang, Yueh Ching Chou, Yuh Lih Chang, Yueh Chien, Kuan Hsuan Chen, Wen Shin Song, Chi Hsien Peng, Chin Hong Chang, Shin Da Lee, Kai Hsi Lu, Yi Jen Chen, Chia Hua Kuo, Chuan Chih Hsu, Hsin Chen Lee, Ming Chi Yung

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)7554-7568
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

Keywords

  • Brown adipocyte
  • C-MYC
  • Induced pluripotent stem cell
  • Peroxisome proliferator-activated receptor gamma coactivator-1α

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

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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. (2011). Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression. International Journal of Molecular Sciences, 12(11), 7554-7568. https://doi.org/10.3390/ijms12117554