Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α overexpression.
Enhanced differentiation of three-gene-reprogrammed induced pluripotent stem cells into adipocytes via adenoviral-mediated PGC-1α overexpression.
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DOI：
10.3390/ijms12117554
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发表时间：
2011
影响因子：
5.6
通讯作者：
Yung MC
中科院分区：
文献类型：
--
作者：
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
仅引入三种因子 Oct4/Sox2/Klf4（3 基因 iPSC）形成的诱导多能干细胞可能为基于干细胞的治疗提供比传统引入四基因 iPSC 的 iPSC 更安全的选择。过氧化物酶体增殖物激活受体 γ 辅激活因子-1α (PGC-1α) 在棕色脂肪发育过程中发挥着重要作用。然而，PGC-1α 在调节线粒体生物发生和 iPSC 分化中的潜在作用仍不清楚。在这里，我们研究了腺病毒介导的 PGC-1α 过表达对 3 基因 iPSC 的影响。 PGC-1α 过度表达导致线粒体质量、活性氧产生和耗氧量增加。基于微阵列的生物信息学表明，PGC-1α 过表达 3 基因 iPSC 的基因表达模式与脂肪细胞中观察到的表达模式相似。此外，PGC-1α过表达增强了脂肪形成分化和多种棕色脂肪标记物的表达，包括解偶联蛋白1、细胞色素C和核呼吸因子1，而抑制了白色脂肪标记物解偶联蛋白2的表达。此外，PGC-1α过表达显着抑制成骨分化。这些数据表明，PGC-1α 指导 3 基因 iPSC 分化为具有棕色脂肪细胞特征的脂肪细胞样细胞。这可能为治疗线粒体疾病和肥胖症提供一种治疗策略。
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.
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影响因子：
14
作者：
Li, Hsin-Yang;Chien, Yueh;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
64.5
作者：
Lin, JD;Wu, PH;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya