Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells.
Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells.
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DOI：
10.1007/s12265-012-9431-2
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发表时间：
2013-02
影响因子：
3.4
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Folmes, Clifford D. L.;Martinez-Fernandez, Almudena;Faustino, Randolph S.;Yamada, Satsuki;Perez-Terzic, Carmen;Nelson, Timothy J.;Terzic, Andre
关键词：
重编程策略影响衍生的诱导多能干细胞的分化能力。去除重编程因子c-Myc可降低iPS细胞的致瘤发生率并增加其生心潜能。C-Myc是能量代谢的调节者，但其对多能诱导下的代谢重编程的影响尚不清楚。在此，对含有(4F)和不含(3F)c-Myc的iPS细胞的线粒体和代谢的询问表明，核重新编程始终将线粒体恢复为类似胚胎的未成熟结构。代谢组学根据获得的多能性相关糖酵解表型从亲代体细胞来源分离来源的iPS细胞，并根据糖酵解中间产物区分3F和4F克隆。实时通量分析表明，在与3F iPS细胞相同的氧化能力设置下，4F iPS细胞具有更强的糖酵解能力。因此，c-Myc的包含增强了衍生iPS细胞的多潜能糖酵解行为，支持不含c-Myc的重编程作为促进氧化代谢依赖的谱系参与的一种策略。
Reprogramming strategies influence the differentiation capacity of derived induced pluripotent stem (iPS) cells. Removal of the reprogramming factor c-Myc reduces tumorigenic incidence and increases cardiogenic potential of iPS cells. c-Myc is a regulator of energy metabolism, yet the impact on metabolic reprogramming underlying pluripotent induction is unknown. Here, mitochondrial and metabolic interrogation of iPS cells derived with (4F) and without (3F) c-Myc demonstrated that nuclear reprogramming consistently reverted mitochondria to embryonic-like immature structures. Metabolomic profiling segregated derived iPS cells from the parental somatic source based on the attained pluripotency-associated glycolytic phenotype and discriminated between 3F versus 4F clones based upon glycolytic intermediates. Real-time flux analysis demonstrated a greater glycolytic capacity in 4F iPS cells, in the setting of equivalent oxidative capacity to 3F iPS cells. Thus, inclusion of c-Myc potentiates the pluripotent glycolytic behavior of derived iPS cells, supporting c-Myc-free reprogramming as a strategy to facilitate oxidative metabolism-dependent lineage engagement.
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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：
14.8
作者：
Bracha, Abigail L.;Ramanathan, Arvind;Huang, Sui;Ingber, Donald E.;Schreiber, Stuart L.
通讯作者：
Schreiber, Stuart L.
影响因子：
64.5
作者：
Cherry AB;Daley GQ
通讯作者：
Daley GQ
DOI：
10.1073/pnas.85.2.339
发表时间：
1988-01-01
影响因子：
11.1
作者：
IZUMO, S;NADALGINARD, B;MAHDAVI, V
通讯作者：
MAHDAVI, V
影响因子：
5.2
作者：
Folmes CDL;Nelson TJ;Dzeja PP;Terzic A
通讯作者：
Terzic A