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.