| First Author | Hwang IY | Year | 2016 |
| Journal | Cell Metab | Volume | 24 |
| Issue | 3 | Pages | 494-501 |
| PubMed ID | 27476977 | Mgi Jnum | J:251898 |
| Mgi Id | MGI:6106935 | Doi | 10.1016/j.cmet.2016.06.014 |
| Citation | Hwang IY, et al. (2016) Psat1-Dependent Fluctuations in alpha-Ketoglutarate Affect the Timing of ESC Differentiation. Cell Metab 24(3):494-501 |
| abstractText | Embryonic stem cells (ESCs) undergo coordinated epigenetic and metabolic changes to differentiate properly. However, the precise mechanisms by which these alterations are fine-tuned in the early stages of differentiation have not been identified. In this study, we demonstrate that phosphoserine aminotransferase 1 (Psat1), an Oct4/Sox2/Nanog (OSN) target protein, regulates changes in alpha-ketoglutarate (alpha-KG), determining the fate of mouse ESCs (mESCs). Maintaining Psat1 levels was essential for mESC self-renewal and pluripotency. Moderate knockdown (KD) of Psat1 in mESCs lowered DNA 5'-hydroxymethylcytosine (5'-hmC) and increased histone methylation levels by downregulating permissive amounts of alpha-KG, ultimately accelerating differentiation. We found that intracellular alpha-KG declined transiently during differentiation and that its dysregulation by treatment with dimethyl-alpha-KG impeded differentiation. Further, by in vivo teratoma formation assay, pluripotency of Psat1 KD mESCs was impaired, especially into the ectodermal lineage. Thus, we have established how Psat1 is regulated in maintaining intracellular alpha-KG levels and determining the fate of mESCs. |
