Center for Regenerative Medicine and Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Cell Metab. 2011 Aug 3;14(2):264-71. doi: 10.1016/j.cmet.2011.06.011.
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.
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，干细胞因子介导的核重编程将线粒体网络逆转为嵴稀少的结构。代谢组学足迹和指纹图谱根据葡萄糖利用的增加和糖酵解终产物的产生，将衍生的多能祖细胞与亲本成纤维细胞区分开来。时间采样表明，在诱导多能标记之前，糖酵解基因的潜能增强。体细胞氧化磷酸化获得的多能糖酵解代谢的功能蜕变符合胚胎样原型。糖酵解的刺激促进了重编程效率，而糖酵解酶活性的阻断则削弱了重编程效率。代谢蛋白质组学解析了决定细胞命运的上调糖酵解酶和下调电子传递链复合物 I 亚基。因此，体细胞的能量基础设施转变为必需的糖酵解代谢类型，为诱导多能性提供燃料。
