Dpto. Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, 46100 Burjassot, Spain.
Janelia Research Campus, Howard Hughes Medical Institute (HHMI), Ashburn, VA 20147, USA.
Stem Cell Reports. 2018 Dec 11;11(6):1479-1492. doi: 10.1016/j.stemcr.2018.10.018. Epub 2018 Nov 21.
Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plasticity necessary for their transition to pluripotency in response to either intrinsic or external cues.
细胞重编程被认为与从氧化代谢到糖酵解代谢的完全代谢转换有关。然而,这种代谢转换的动态变化及其控制因素尚未完全了解。通过使用细胞、生化、蛋白质阵列、代谢组学和呼吸测定分析,我们发现 c-MYC 在细胞重编程早期建立了一个强大的二价能量程序。易于进行重编程的细胞表现出线粒体膜电位高,并显示出混合代谢。我们的结论是,MYC 蛋白在细胞重编程早期协调体细胞代谢的重排,从而使体细胞获得对内在或外在信号作出反应向多能性转变所必需的表型可塑性。