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Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications.
Life Science Alliance ( IF 4.4 ) Pub Date : 2019-09-27 , DOI: 10.26508/lsa.201900413
Shengya Tian 1, 2 , Junru Feng 2 , Yang Cao 2 , Shengqi Shen 2 , Yongping Cai 3 , Dongdong Yang 2 , Ronghui Yan 2 , Lihua Wang 2 , Huafeng Zhang 2 , Xiuying Zhong 4 , Ping Gao 2, 4, 5
Affiliation  

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.

中文翻译:

甘氨酸裂解系统通过衰老和表观遗传修饰的调控决定多能干细胞的命运。

代谢重塑已成为干细胞多能性的关键。但是,其潜在机制尚未完全阐明。在这里,我们发现甘氨酸裂解系统(GCS)被高度激活以促进干细胞多能性和体细胞重编程过程中。从机制上讲,我们揭示了由Sox2和Lin28A调节的限速GCS酶Gldc的表达促进了这种激活。我们进一步发现,活化的GCS会催化甘氨酸代谢以促进H3K4me3修饰,从而促进多能性基因的表达。此外,活化的GCS有助于裂解过量的甘氨酸并防止甲基乙二醛积聚,从而刺激干细胞和重编程过程中的衰老。总的来说,
更新日期:2020-08-21
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