State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PRC ; State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PRC.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Stem Cell Reports. 2014 Feb 27;2(3):253-61. doi: 10.1016/j.stemcr.2014.01.012. eCollection 2014 Mar 11.
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.
体细胞重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应用前景。然而，传统定义因子（OSMK）介导的重编程过程非常缓慢且效率极低。在这里，我们开发了一种改良的重编程因子（OySyNyK）组合，其中 Yes 相关蛋白的转录激活结构域融合到定义因子中，并建立了一种高效快速的重编程系统。我们发现，OySyNyK 诱导的 iPSCs 的效率比 OSNK 高 100 倍，并且 OySyNyK 的重编程非常迅速，在 24 小时内即可启动。我们发现 OySyNyK 因子在早期显著增加 Tet1 的表达，并与 Tet1/2 相互作用以促进重编程。我们的研究不仅建立了一个快速而高效的 iPSC 重编程系统，还揭示了工程化因子与 TETs 协调以调节 5hmC 介导的表观遗传控制的机制。
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