Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway.
Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K/AKT signal pathway.
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DOI：
10.1016/j.biomaterials.2012.04.001
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发表时间：
2012-08
期刊：
影响因子：
14
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Chen M;Zhang H;Wu J;Xu L;Xu D;Sun J;He Y;Zhou X;Wang Z;Wu L;Xu S;Wang J;Jiang S;Zhou X;Hoffman AR;Hu X;Hu J;Li T
通过确定的因素从体细胞产生诱导多能干细胞（iPSC）是一种机制未知但极其耗时的过程。低效率的重编程导致体外iPSC选择的时间延长，导致微妙的遗传和表观遗传异常。为了促进多能重编程，我们已经确定了甲状腺激素三碘甲状腺原氨酸（T3）作为一种内源性因子，可以增强人皮肤成纤维细胞（HDF）和脐带间充质干细胞（UCMSC）的重编程。iPSC诱导的这种增强与代谢重塑活性相关，包括关键糖酵解基因的上调、细胞增殖的增加和间充质-上皮转化（MET）的诱导。我们进一步确定了T3对PI3K/AKT信号通路的激活是该模型中细胞多能性转化增强的潜在机制。这些研究表明，T3在增强细胞重编程中增强供体细胞的代谢重塑。
Generation of induced pluripotent stem cells (iPSCs) from somatic cells by defined factors is a mechanism-unknown, yet extremely time-consuming process. Inefficient reprogramming leads to prolonged periods of in vitro iPSC selection, resulting in subtle genetic and epigenetic abnormalities. To facilitate pluripotent reprogramming, we have identified the thyroid hormone triiodothyronine (T3) as an endogenous factor that can enhance reprogramming of human dermal fibroblasts (HDF) and umbilical cord mesenchymal stem cells (UCMSC). This potentiation of iPSC induction is associated with metabolic remodeling activity, including up-regulation of key glycolytic genes, an increase in cell proliferation, and the induction of mesenchymal-epithelial transition (MET). We further identify the activation of the PI3K/AKT signal pathway by T3 as an underlying mechanism for the enhanced conversion to cell pluripotency in this model. These studies demonstrate that T3 enhances metabolic remodeling of donor cells in potentiating cell reprogramming.
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影响因子：
48
作者：
Lin, Tongxiang;Ambasudhan, Rajesh;Yuan, Xu;Li, Wenlin;Hilcove, Simon;Abujarour, Ramzey;Lin, Xiangyi;Hahm, Heung Sik;Hao, Ergeng;Hayek, Alberto;Ding, Sheng
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Ding, Sheng
影响因子：
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Zhang, Kun
影响因子：
4.8
作者：
Hu, JF;Vu, TH;Hoffman, AR
通讯作者：
Hoffman, AR
影响因子：
5.6
作者：
Becker, Klaus A.;Ghule, Prachi N.;Stein, Gary S.
通讯作者：
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影响因子：
29
作者：
Folmes CD;Nelson TJ;Martinez-Fernandez A;Arrell DK;Lindor JZ;Dzeja PP;Ikeda Y;Perez-Terzic C;Terzic A
通讯作者：
Terzic A