誘導多能幹細胞（iPSc）技術自誕生之日起就受到了人們極大關注。但是誘導多能幹細胞是一個耗時長、效率極低的過程，其需要2至3周誘導時間，效率只有0.01-1%。並且對於其機制目前也研究得不是很透徹。iPS技術要真正走向臨床應用還有許多問題亟待解決，如深入了解其機制、提高誘導效率、縮短誘導時間和提高安全性。
由中國科學院動物研究所研究員陳大華和孫欽秒以及Emory大學教授金鵬領導的研究團隊，將轉錄共激活因子YAP的轉錄激活結構域（TAD）和Oct4、Sox2、Nanog分別進行融合。這種融合了激活結構域的誘導方法（OySyNyK-iPS）和傳統的誘導方法（OSNK-iPS）相比，可以更加快速、高效地誘導體細胞重編程。OySyNyK-iPS誘導方法可以在轉染後24小時左右就觀測到Oct4-GFP報告基因的表達，3-4天就有初步的iPS克隆形成，6-7天就可以挑取iPS克隆進行建系傳代，而傳統的OSNK-iPS方法則需要兩周左右的時間才能進行建系傳代。並且該融合因子方法iPS誘導效率比傳統OSNK-iPS誘導方法高達100倍左右。進一步機制研究表明Tet1/2在體細胞重編程早期過程中起著重要作用，Tet1/2表達水平和5hmC的水平在iPS形成過程中都呈上升趨勢。在iPCs形成過程中，敲低Tet1或者Tet2的表達都顯著地降低iPS的重編程效率。同時該研究還發現Sox2、Nanog可以和Tet1/2相互作用，因此可以影響Tet1/2蛋白在多能性基因啟動子區域的定位，並通過去甲基化方式激活多能性基因的表達。
該成果近日發表在Cell旗下的Stem Cell Reports雜誌上。（生物谷Bioon.com）
生物谷推薦的英文摘要
Stem Cell Reports doi：10.1016/j.stemcr.2014.01.012
Coordination of Engineered Factors with TET1/2 Promotes Early-Stage Epigenetic Modification during Somatic Cell Reprogramming
Gengzhen Zhu， Yujing Li， Fei Zhu， Tao Wang， Wensong Jin， Wei Mu， Wei Lin， Weiqi Tan， Wenqi Li， R. Craig Street， Siying Peng， Jian Zhang， Yue Feng， Stephen T. Warren， Qinmiao Sun， Peng Jin， Dahua Chen
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.