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 |
|---|---|
| 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 |
指紋
ASJC Scopus subject areas
- Computer Science Applications
- Molecular Biology
- Catalysis
- Inorganic Chemistry
- Spectroscopy
- Organic Chemistry
- Physical and Theoretical Chemistry
- Medicine(all)
引用此文
Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression. / 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.
於: International Journal of Molecular Sciences, 卷 12, 編號 11, 11.2011, p. 7554-7568.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression
AU - Huang, Pin I.
AU - Chou, Yueh Ching
AU - Chang, Yuh Lih
AU - Chien, Yueh
AU - Chen, Kuan Hsuan
AU - Song, Wen Shin
AU - Peng, Chi Hsien
AU - Chang, Chin Hong
AU - Lee, Shin Da
AU - Lu, Kai Hsi
AU - Chen, Yi Jen
AU - Kuo, Chia Hua
AU - Hsu, Chuan Chih
AU - Lee, Hsin Chen
AU - Yung, Ming Chi
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Brown adipocyte
KW - C-MYC
KW - Induced pluripotent stem cell
KW - Peroxisome proliferator-activated receptor gamma coactivator-1α
UR - http://www.scopus.com/inward/record.url?scp=82255181749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82255181749&partnerID=8YFLogxK
U2 - 10.3390/ijms12117554
DO - 10.3390/ijms12117554
M3 - Article
C2 - 22174616
AN - SCOPUS:82255181749
VL - 12
SP - 7554
EP - 7568
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
ER -