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

International Journal of Molecular Sciences

Pin-I Huang⁴  Yueh-Ching Chou⁶  Yuh-Lih Chang⁶  Yueh Chien⁶  Kuan-Hsuan Chen⁴  Wen-Shin Song³  Chi-Hsien Peng⁴  Chin-Hong Chang⁵  Shin-Da Lee¹  Kai-Hsi Lu³  Yi-Jen Chen³  Chia-Hua Kuo²  Chuan-Chih Hsu⁵  Hsin-Chen Lee⁶ 

[1] Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung 404, Taiwan; E-Mail:;Laboratory of Exercise Biochemistry, Taipei Physical Education College, Taipei 111, Taiwan; E-Mail:;School of Medicine, National Yang-Ming University, Taipei 112, Taiwan; E-Mails:;Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan; E-Mails:;Department of Surgery, Chi-Mei Medical Center, Tainan 710, Taiwan; E-Mails:;Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan; E-Mails:

关键词: induced pluripotent stem cell;    c-Myc;    peroxisome proliferator-activated receptor gamma coactivator-1α;    brown adipocyte;   

DOI  :  10.3390/ijms12117554

来源: mdpi

【 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 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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.