Journal
METABOLIC ENGINEERING
Volume 53, Issue -, Pages 35-47Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2019.02.003
Keywords
Glycine decarboxylase (GLDC); Pluripotent stem cell; Glycolysis; Methylglyoxal; Advanced glycation end product (AGE); Reprogramming
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Funding
- Bio & Medical Technology Development Program of the National Research Foundation (NRF, South Korea) - Ministry of Science and ICT, South Korea [NRF-2014M3A9D3034158, NRF-2015M3A9B4071074]
- Institute of Animal Molecular Biotechnology Grant
- School of Life Sciences and Biotechnology for BK21 PLUS, Korea University
- National Research Foundation of Korea [2014M3A9D3034158, 2015M3A9B4071074] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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