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

研究成果: 雜誌貢獻文章

7 引文 (Scopus)

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
12
發行號11
DOIs
出版狀態已發佈 - 十一月 2011
對外發佈Yes

指紋

Induced Pluripotent Stem Cells
stem cells
Stem cells
Adipocytes
genes
Oils and fats
Genes
Fats
fats
Brown Adipose Tissue
Proteins
Nuclear Respiratory Factor 1
Brown Adipocytes
Mitochondrial Diseases
White Adipose Tissue
Oxygen
markers
Organelle Biogenesis
Cytochromes
Bioinformatics

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

Huang, PI, Chou, YC, Chang, YL, Chien, Y, Chen, KH, Song, WS, Peng, CH, Chang, CH, Lee, SD, Lu, KH, Chen, YJ, Kuo, CH, Hsu, CC, Lee, HC & Yung, MC 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, 卷 12, 編號 11, 頁 7554-7568. https://doi.org/10.3390/ijms12117554
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. / Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression. 於: International Journal of Molecular Sciences. 2011 ; 卷 12, 編號 11. 頁 7554-7568.
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title = "Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α over expression",
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.",
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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

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KW - Peroxisome proliferator-activated receptor gamma coactivator-1α

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