O-GlcNAc Regulates Pluripotency and Reprogramming by Directly Acting on Core Components of the Pluripotency Network
- Authors
- Jang, H[Jang, Hyonchol]; Kim, TW[Kim, Tae Wan]; Yoon, S[Yoon, Sungho]; Choi, SY[Choi, Soo-Youn]; Kang, TW[Kang, Tae-Wook]; Kim, SY[Kim, Seon-Young]; Kwon, YW[Kwon, Yoo-Wook]; Cho, EJ[Cho, Eun-Jung]; Youn, HD[Youn, Hong-Duk]
- Issue Date
- 6-Jul-2012
- Publisher
- CELL PRESS
- Citation
- CELL STEM CELL, v.11, no.1, pp.62 - 74
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL STEM CELL
- Volume
- 11
- Number
- 1
- Start Page
- 62
- End Page
- 74
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/64837
- DOI
- 10.1016/j.stem.2012.03.001
- ISSN
- 1934-5909
- Abstract
- O-linked-N-acetylglucosamine (O-GlcNAc) has emerged as a critical regulator of diverse cellular processes, but its role in embryonic stem cells (ESCs) and pluripotency has not been investigated. Here we show that O-GlcNAcylation directly regulates core components of the pluripotency network. Blocking O-GlcNAcylation disrupts ESC self-renewal and reprogramming of somatic cells to induced pluripotent stem cells. The core reprogramming factors Oct4 and Sox2 are O-GlcNAcylated in ESCs, but the O-GlcNAc modification is rapidly removed upon differentiation. O-GlcNAc modification of threonine 228 in Oct4 regulates Oct4 transcriptional activity and is important for inducing many pluripotency-related genes, including Klf2, Klf5, Nr5a2, Tbx3, and Tcl1. A T228A point mutation that eliminates this O-GlcNAc modification reduces the capacity of Oct4 to maintain ESC self-renewal and reprogram somatic cells. Overall, our study makes a direct connection between O-GlcNAcylation of key regulatory transcription factors and the activity of the pluripotency network.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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