Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control

Phil Jun Kang, Jie Zheng, Gilju Lee, Daryeon Son, In Yong Kim, Gwonhwa Song, Gyuman Park, Seungkwon You

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)35-47
Number of pages13
JournalMetabolic Engineering
Volume53
DOIs
Publication statusPublished - 2019 May 1

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Keywords

  • Advanced glycation end product (AGE)
  • Glycine decarboxylase (GLDC)
  • Glycolysis
  • Methylglyoxal
  • Pluripotent stem cell
  • Reprogramming

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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