S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Biomedical Sciences (대학원 의과학과) Theses (Ph.D. / Sc.D._의과학과)
The effect of phosphoserine aminotransferase-1 dependent fluctuation on timing of embryonic stem cell differentiation
- 의과대학 의과학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과학과, 2016. 8. 윤홍덕.
- Embryonic stem cells (ESCs) undergo coordinated epigenetic and metabolic changes to differentiate properly. However, the precise mechanisms by which these alterations are finely tuned at early stages of differentiation have not been identified. In this study, we demonstrate that phosphoserine aminotransferase 1 (Psat1), an Oct4/Sox2/Nanog target protein that regulates changes in α-ketoglutarate (α-KG), determines the fate of mESCs. Maintaining Psat1 level was essential for mESCs self-renewal and pluripotency. Moderate Psat1 knockdown mESCs had decreased DNA 5-hydroxymethylation (5-hmC) and increased histone methylation levels by downregulating permissive amounts of α-KG, ultimately accelerating differentiation. We found that intracellular α-KG transiently declined during differentiation and its disturbance by treatment with dimethyl-α-KG (dm-α-KG) delayed differentiation. Further, in vivo teratoma formation assay showed impaired pluripotency of Psat1 knockdown mESCs especially into ectodermal lineage. Altogether, we reveal how Psat1 is regulated to maintain intracellular α-KG and the fate of mESCs