Coordination of engineered factors with TET1/2 promotes early-stage epigenetic modification during somatic cell reprogramming.
Coordination of engineered factors with TET1/2 promotes early-stage epigenetic modification during somatic cell reprogramming.
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工程因子与 TET1/2 的协调促进体细胞重编程过程中的早期表观遗传修饰
DOI：
10.1016/j.stemcr.2014.01.012
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发表时间：
2014-03-11
影响因子：
5.9
通讯作者：
Chen, Dahua
中科院分区：
文献类型：
--
作者：
Zhu, Gengzhen;Li, Yujing;Zhu, Fei;Wang, Tao;Jin, Wensong;Mu, Wei;Lin, Wei;Tan, Weiqi;Li, Wenqi;Street, R. Craig;Peng, Siying;Zhang, Jian;Feng, Yue;Warren, Stephen T.;Sun, Qinmiao;Jin, Peng;Chen, Dahua
体细胞重新编程为诱导多能干细胞(IPSCs)在未来的再生医学中具有巨大的前景。然而，由传统的定义因子(OSMK)介导的重编程过程缓慢且效率极低。在这里，我们开发了一个修改的重编程因子(OySyNyK)的组合，其中Yes相关蛋白的反式激活结构域与定义的因子融合在一起，并建立了一个高效和快速的重编程系统。我们发现，OySyNyK诱导的IPSCs的效率是OSNK的100倍，并且OySyNyK的重编程非常迅速，在24小时内启动。我们发现OySyNyK因子在早期显著增加Tet1的表达，并与Tet1/2相互作用促进重编程。我们的研究不仅建立了一个快速高效的IPSC重编程系统，还揭示了一种工程因子与Tets协同调控5hmC介导的表观遗传控制的机制。建立了一个高效、快速的重编程系统，TET1/2蛋白参与了OySyNyK对IPSC的快速诱导，OySyNyK因子与Tet蛋白协同促进快速重编程，传统的定义因子(OSMK)介导的重编程过程缓慢而低效。孙、金、陈和他的同事开发了一种修改的重编程因子(OySyNyK)的组合，其中Yes相关蛋白的反式激活结构域与定义的因子融合在一起，并建立了一个高效和快速的重编程系统。
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. A combination of modified reprogramming factors (OySyNyK) is developed A highly efficient and rapid reprogramming system is established TET1/2 proteins are involved in rapid iPSC induction by OySyNyK OySyNyK factors coordinate with TET proteins to promote rapid reprogramming The reprogramming process mediated by the traditional defined factors (OSMK) is slow and inefficient. Sun, Jin, Chen, and colleagues have developed 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.
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影响因子：
23.9
作者：
Dawlaty, Meelad M.;Ganz, Kibibi;Powell, Benjamin E.;Hu, Yueh-Chiang;Markoulaki, Styliani;Cheng, Albert W.;Gao, Qing;Kim, Jongpil;Choi, Sang-Woon;Page, David C.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
48
作者：
Lin, Tongxiang;Ambasudhan, Rajesh;Yuan, Xu;Li, Wenlin;Hilcove, Simon;Abujarour, Ramzey;Lin, Xiangyi;Hahm, Heung Sik;Hao, Ergeng;Hayek, Alberto;Ding, Sheng
通讯作者：
Ding, Sheng
影响因子：
64.5
作者：
Young RA
通讯作者：
Young RA
影响因子：
16
作者：
Piccolo, Francesco M.;Bagci, Hakan;Brown, Karen E.;Landeira, David;Soza-Ried, Jorge;Feytout, Amelie;Mooijman, Dylan;Hajkova, Petra;Leitch, Harry G.;Tada, Takashi;Kriaucionis, Skirmantas;Dawlaty, Meelad M.;Jaenisch, Rudolf;Merkenschlager, Matthias;Fisher, Amanda G.
通讯作者：
Fisher, Amanda G.
DOI：
10.1126/science.1172482
发表时间：
2009-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yu J;Hu K;Smuga-Otto K;Tian S;Stewart R;Slukvin II;Thomson JA
通讯作者：
Thomson JA