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.