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

doi:10.1016/j.ymben.2019.02.003

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

Department of Biotechnology

Research output: Contribution to journal › Article › peer-review

17 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 language	English
Pages (from-to)	35-47
Number of pages	13
Journal	Metabolic engineering
Volume	53
DOIs	https://doi.org/10.1016/j.ymben.2019.02.003
Publication status	Published - 2019 May

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF, South Korea) funded by the Ministry of Science and ICT, South Korea [NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University.

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation ( NRF, South Korea ) funded by the Ministry of Science and ICT, South Korea [ NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074 ], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University. Appendix A

Publisher Copyright:
© 2019

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymben.2019.02.003

Cite this

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title = "Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control",

abstract = "Reprogramming of {\textquoteleft}adult{\textquoteright} differentiated somatic cells to {\textquoteleft}embryonic{\textquoteright} 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.",

keywords = "Advanced glycation end product (AGE), Glycine decarboxylase (GLDC), Glycolysis, Methylglyoxal, Pluripotent stem cell, Reprogramming",

author = "Kang, {Phil Jun} and Jie Zheng and Gilju Lee and Daryeon Son and Kim, {In Yong} and Gwonhwa Song and Gyuman Park and Seungkwon You",

note = "Funding Information: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF, South Korea) funded by the Ministry of Science and ICT, South Korea [NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University. Funding Information: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation ( NRF, South Korea ) funded by the Ministry of Science and ICT, South Korea [ NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074 ], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University. Appendix A Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = may,

doi = "10.1016/j.ymben.2019.02.003",

language = "English",

volume = "53",

pages = "35--47",

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AU - Kang, Phil Jun

AU - Zheng, Jie

AU - Lee, Gilju

AU - Son, Daryeon

AU - Kim, In Yong

AU - Song, Gwonhwa

AU - Park, Gyuman

AU - You, Seungkwon

N1 - Funding Information: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF, South Korea) funded by the Ministry of Science and ICT, South Korea [NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University. Funding Information: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation ( NRF, South Korea ) funded by the Ministry of Science and ICT, South Korea [ NRF-2014M3A9D3034158 and NRF-2015M3A9B4071074 ], Institute of Animal Molecular Biotechnology Grant, and School of Life Sciences and Biotechnology for BK21 PLUS, Korea University. Appendix A Publisher Copyright: © 2019

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N2 - 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.

AB - 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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KW - Methylglyoxal

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SN - 1096-7176

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SP - 35

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JO - Metabolic engineering

JF - Metabolic engineering

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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