期刊
LIFE SCIENCE ALLIANCE
卷 2, 期 5, 页码 -出版社
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.201900413
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资金
- National Key R&D Program of China [2018YFA0800300, 2018YFA0107103, 2017YFA0205600]
- National Natural Science Foundation of China [81525022, 31571472, 81530076, 81821001]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDPB10]
- Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology [2017FXZY004]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S054]
Metabolic remodelling has emerged as critical for stem cell pluripotency; however, the underlying mechanisms have yet to be fully elucidated. Here, we found that the glycine cleavage system (GCS) is highly activated to promote stem cell pluripotency and during somatic cell reprogramming. Mechanistically, we revealed that the expression of Gldc, a rate-limiting GCS enzyme regulated by Sox2 and Lin28A, facilitates this activation. We further found that the activated GCS catabolizes glycine to fuel H3K4me3 modification, thus promoting the expression of pluripotency genes. Moreover, the activated GCS helps to cleave excess glycine and prevents methylglyoxal accumulation, which stimulates senescence in stem cells and during reprogramming. Collectively, our results demonstrate a novel mechanism whereby GCS activation controls stem cell pluripotency by promoting H3K4me3 modification and preventing cellular senescence.
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