Coordination of Engineered Factors with TET1/2 Promotes Early-Stage Epigenetic Modification during Somatic Cell Reprogramming

• Type of Material: Article
• Authors: Gengzhen Zhu, Chinese Academy of Sciences; Yujing Li, Emory University; Fei Zhu, Chinese Academy of Sciences; Tao Wang, Emory University; Wensong Jin, Chinese Academy of Sciences; Wei Mu, Chinese Academy of Sciences; Wei Lin, Chinese Academy of Sciences; Weiqi Tan, Chinese Academy of Sciences; Wenqi Li, Emory University; R. Craig Street, Emory University; Siying Peng, Beijing Biocytogen Co., Ltd; Jian Zhang, Chinese Academy of Sciences; Yue Feng, Emory University; Stephen Warren, Emory University; Qinmiao Sun, Chinese Academy of Sciences; Peng Jin, Emory University; Dahua Chen, Chinese Academy of Sciences
• Language: English
• Date: 2014-03
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2014 The Authors
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.stemcr.2014.01.012
• Title of Journal or Parent Work: Stem Cell Reports
• ISSN: 2213-6711
• Volume: 2
• Issue: 3
• Start Page: 253
• End Page: 261
• Grant/Funding Information: This study was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01010306), National Basic Research Program of China (2013CB945000), and Natural Science Foundation of China (91019022, 31130036, and 31329004) and in part by the National Institutes of Health (grants NS079625 and HD073162, to P.J.; grants MH089606 and HD24064, to S.T.W.) and the Emory Genetics Discovery Fund.
• Research Categories: Biology, Genetics; Health Sciences, Pharmacology

Abstract

Summary Somatic cell reprogramming toward induced pluripotent stem cells (iPSCs) holds great promise in future regenerative medicine. However, the reprogramming process mediated by the traditional defined factors (OSMK) is slow and extremely inefficient. Here, we develop a combination of modified reprogramming factors (OySyNyK) in which the transactivation domain of the Yes-associated protein is fused to defined factors and establish a highly efficient and rapid reprogramming system. We show that the efficiency of OySyNyK-induced iPSCs is up to 100-fold higher than the OSNK and the reprogramming by OySyNyK is very rapid and is initiated in 24 hr. We find that OySyNyK factors significantly increase Tet1 expression at the early stage and interact with Tet1/2 to promote reprogramming. Our studies not only establish a rapid and highly efficient iPSC reprogramming system but also uncover a mechanism by which engineered factors coordinate with TETs to regulate 5hmC-mediated epigenetic control.