Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control
Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control
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DOI：
10.1016/j.ymben.2019.02.003
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发表时间：
2019-05-01
影响因子：
8.4
通讯作者：
You, Seungkwon
中科院分区：
文献类型：
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作者：
Kang, Phil Jun;Zheng, Jie;You, Seungkwon
将“成人”分化的体细胞重编程为“胚胎”多能干细胞，并伴随糖酵解速率增加。相反，糖酵解通过促进甲基乙二醛的产生触发晚期糖基化终产物（AGEs）的积累，AGEs是衰老的潜在致病因素。因此，多能干细胞（PSC）可以特异性地调节糖酵解以维持其胚胎特征。在这项研究中，我们专注于甘氨酸脱羧酶（GLDC），甘氨酸裂解系统中的一个关键酶，调节糖酵解和甲基乙二醛在癌症中的生产。GLDC仅在PSC中表达，并且抑制这种酶诱导代谢组和AGE积累的改变，从而抑制胚胎多能状态。令人惊讶的是，体细胞中积累的AGEs水平在重编程过程中逐渐下降，最终在iPSC中消失。此外，GLDC的异位表达或用AGE抑制剂LR-90处理促进了重编程。总之，这些发现表明GLDC介导的糖酵解调节和控制AGE积累与多能性的维持和诱导有关。
Reprogramming of 'adult' differentiated somatic cells to 'embryonic' pluripotent stem cells accompanied by increased rate of glycolysis. Conversely, glycolysis triggers accumulation of advanced glycation end products (AGEs), a potential causative factor in aging, by promoting methylglyoxal production. Therefore, it is reasonable that pluripotent stem cells (PSCs) would specifically regulate glycolysis to maintain their embryonic features. In this study, we focused on glycine decarboxylase (GLDC), a key enzyme in the glycine cleavage system that regulates glycolysis and methylglyoxal production in cancer. GLDC was exclusively expressed in PSCs, and inhibition of this enzyme induced alterations of metabolome and AGE accumulation, thereby suppressing the embryonic pluripotent state. Surprisingly, the level of accumulated AGEs in somatic cells gradually decreased during reprogramming, ultimately disappearing in iPSCs. In addition, ectopic expression of GLDC or treatment with the AGE inhibitor LR-90 promoted reprogramming. Together, these findings suggest that GLDC-mediated regulation of glycolysis and controlling AGE accumulation is related to maintenance and induction of pluripotency.