한빛사논문
- 조회3,310
Abstract
In-Young Hwang1, 2, Sojung Kwak1, 2, Sangho Lee1, 9, Hyunsoo Kim1, 2, Sang Eun Lee5, Jae-Hwan Kim1, 2, 3, Young Ah Kim1, 9, Yoon Kyung Jeon4, Doo Hyun Chung2, 4, Xing Jin6, Sunghyouk Park6, Hyonchol Jang7, Eun-Jung Cho8, Hong-Duk Youn1, 2, 3, 9, 10,*
1 National Creative Research Center for Epigenome Reprogramming Network, Seoul National University Hospital, Seoul 03080, Republic of Korea
2 Department of Biomedical Sciences, Seoul National University Hospital, Seoul 03080, Republic of Korea
3 Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
4 Department of Pathology, Seoul National University Hospital, Seoul 03080, Republic of Korea
5 Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea
6 College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Republic of Korea
7 Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
8 College of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
9 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea
10 Lead Contact
*Corresponding author : Hong-Duk Youn
Summary
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 α-ketoglutarate (α-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 α-KG, ultimately accelerating differentiation. We found that intracellular α-KG declined transiently during differentiation and that its dysregulation by treatment with dimethyl-α-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 α-KG levels and determining the fate of mESCs.
논문정보
- Research article
- 2016년 07월 (BRIC 등록일 2016-08-10)
- 국내 연구진
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