体细胞可以通过外源因子的表达被重新编程为具有多能性，这些外源因子一般包括Oct4、Sox2、Klf4 和Myc (OSKM)。在重新编程过程中，只有一小部分的细胞转化成“诱导多能干”(iPS) 细胞。阻止大多数细胞转变成iPS细胞的障碍物的性质尚不清楚，同时我们也不知道是否能让iPS细胞重新编程变得具有确定性和高效率。现在，Jacob Hanna及其同事发现，高效转换是可能的。他们发现，将2i/LIF生长条件和OSKM过度表达相结合，再加上使Mbd3/NuRD co-repressor中和，向多能性的确定性的、同步的重新编程就会出现。仅仅经过7天时间的OSKM诱导，几乎100%的小鼠和人类体细胞就转变成了初始的iPS细胞。(生物谷Bioon.com)
生物谷推荐英文摘要
Nature doi:10.1038/nature12587
Deterministic direct reprogramming of somatic cells to pluripotency
Yoach Rais, Asaf Zviran,Shay Geula,Ohad Gafni,Elad Chomsky,Sergey Viukov,Abed AlFatah Mansour,Inbal Caspi,Vladislav Krupalnik,Mirie Zerbib,Itay Maza,Nofar Mor,Dror Baran,Leehee Weinberger,Diego A. Jaitin,David Lara-Astiaso,Ronnie Blecher-Gonen,Zohar Shipony,Zohar Mukamel,Tzachi Hagai,Shlomit Gilad, Daniela Amann-Zalcenstein,Amos Tanay,Ido Amit,Noa Novershtern,et al.
Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem (iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.
