Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.
Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming.
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DOI：
10.1016/j.cmet.2011.06.011
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发表时间：
2011-08-03
期刊：
影响因子：
29
通讯作者：
Terzic A
中科院分区：
文献类型：
--
作者：
Folmes CD;Nelson TJ;Martinez-Fernandez A;Arrell DK;Lindor JZ;Dzeja PP;Ikeda Y;Perez-Terzic C;Terzic A
体细胞去分化为诱导多能干细胞的生物能量学在很大程度上仍然未知。在这里，干性因子介导的核重编程将线粒体网络恢复为嵴贫乏的结构。代谢足迹法和指纹法根据升高的葡萄糖利用率和糖酵解终产物的产生将衍生的多能后代与亲本成纤维细胞区分开。时间采样证明糖酵解基因增强诱导多能标记物之前。体细胞氧化磷酸化到获得性多能糖酵解代谢的功能变态符合胚胎样原型。糖酵解的刺激促进了重编程效率，而糖酵解酶活性的阻断使重编程效率减弱。代谢蛋白质组学解决上调糖酵解酶和下调电子传递链复合物I亚基的细胞命运决定。因此，体细胞的能量基础结构转变成所需的糖酵解代谢型以促进多能性的诱导。
The bioenergetics of somatic dedifferentiation into induced pluripotent stem cells remains largely unknown. Here, stemness factor mediated nuclear reprogramming reverted mitochondrial networks into cristae-poor structures. Metabolomic footprinting and fingerprinting distinguished derived pluripotent progeny from parental fibroblasts according to elevated glucose utilization and production of glycolytic end products. Temporal sampling demonstrated glycolytic gene potentiation prior to induction of pluripotent markers. Functional metamorphosis of somatic oxidative phosphorylation into acquired pluripotent glycolytic metabolism conformed to an embryonic-like archetype. Stimulation of glycolysis promoted, while blockade of glycolytic enzyme activity blunted, reprogramming efficiency. Metaboproteomics resolved upregulated glycolytic enzymes and downregulated electron transport chain complex I subunits underlying cell fate determination. Thus, the energetic infrastructure of somatic cells transitions into a required glycolytic metabotype to fuel induction of pluripotency.
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影响因子：
5
作者：
Chung S;Arrell DK;Faustino RS;Terzic A;Dzeja PP
通讯作者：
Dzeja PP
影响因子：
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作者：
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影响因子：
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作者：
Dzeja PP;Chung S;Faustino RS;Behfar A;Terzic A
通讯作者：
Terzic A
影响因子：
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作者：
Perez-Terzic, Carmen;Faustino, Randolph S;Terzic, Andre
通讯作者：
Terzic, Andre
影响因子：
9.7
作者：
Ko, YH;Pedersen, PL;Geschwind, JF
通讯作者：
Geschwind, JF