Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State.
Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State.
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DOI：
10.1016/j.stem.2016.08.008
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发表时间：
2016-10-06
期刊：
影响因子：
23.9
通讯作者：
Christofk, Heather R.
中科院分区：
文献类型：
--
作者：
Gu, Wen;Gaeta, Xavier;Sahakyan, Anna;Chan, Alanna B.;Hong, Candice S.;Kim, Rachel;Braas, Daniel;Plath, Kathrin;Lowry, William E.;Christofk, Heather R.
糖酵解代谢的速率在人胚胎干细胞（hESC）分化和体细胞重编程为多能性的过程中发生变化。然而，糖酵解代谢对多能状态的功能贡献尚不清楚。在这里，我们表明，幼稚的hESC表现出增加的糖酵解通量，MYC转录活性，和核N-MYC定位相对于引发的hESC。这种状态与人胚泡的内细胞团一致，其中MYC转录活性和核N-MYC水平也高于致敏的hESC。糖酵解的减少降低了幼稚hESC和无饲养层的致敏hESC的自我更新，但在饲养层支持的条件下生长的致敏hESC没有。无饲养层的致敏hESC中糖酵解的减少也增强了神经特化。这些发现揭示了糖酵解代谢和人类幼稚多能性之间的关联以及饲养层/无饲养层培养的hESC的代谢差异。他们还可能建议用于调节hESC的自我更新和初始细胞命运特化的方法。
The rate of glycolytic metabolism changes during differentiation of human embryonic stem cells (hESCs) and reprogramming of somatic cells to pluripotency. However, the functional contribution of glycolytic metabolism to the pluripotent state is unclear. Here we show that naive hESCs exhibit increased glycolytic flux, MYC transcriptional activity, and nuclear N-MYC localization relative to primed hESCs. This status is consistent with the inner cell mass of human blastocysts, where MYC transcriptional activity and nuclear N-MYC levels are also higher than in primed hESCs. Reduction of glycolysis decreases self-renewal of naive hESCs and feeder-free primed hESCs, but not primed hESCs grown in feeder-supported conditions. Reduction of glycolysis in feeder-free primed hESCs also enhances neural specification. These findings reveal associations between glycolytic metabolism and human naive pluripotency and differences in the metabolism of feeder-/feeder-free cultured hESCs. They may also suggest methods for regulating self-renewal and initial cell fate specification of hESCs.
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