RT Journal Article SR Electronic T1 Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900413 DO 10.26508/lsa.201900413 VO 2 IS 5 A1 Tian, Shengya A1 Feng, Junru A1 Cao, Yang A1 Shen, Shengqi A1 Cai, Yongping A1 Yang, Dongdong A1 Yan, Ronghui A1 Wang, Lihua A1 Zhang, Huafeng A1 Zhong, Xiuying A1 Gao, Ping YR 2019 UL http://www.life-science-alliance.org/content/2/5/e201900413.abstract 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.