PT - JOURNAL ARTICLE AU - Tian, Shengya AU - Feng, Junru AU - Cao, Yang AU - Shen, Shengqi AU - Cai, Yongping AU - Yang, Dongdong AU - Yan, Ronghui AU - Wang, Lihua AU - Zhang, Huafeng AU - Zhong, Xiuying AU - Gao, Ping TI - Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications AID - 10.26508/lsa.201900413 DP - 2019 Oct 01 TA - Life Science Alliance PG - e201900413 VI - 2 IP - 5 4099 - http://www.life-science-alliance.org/content/2/5/e201900413.short 4100 - http://www.life-science-alliance.org/content/2/5/e201900413.full SO - Life Sci. Alliance2019 Oct 01; 2 AB - 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.