體細(xì)胞可以通過外源因子的表達(dá)被重新編程為具有多能性,，這些外源因子一般包括Oct4,、Sox2、Klf4 和Myc (OSKM),。在重新編程過程中,，只有一小部分的細(xì)胞轉(zhuǎn)化成“誘導(dǎo)多能干”(iPS) 細(xì)胞。阻止大多數(shù)細(xì)胞轉(zhuǎn)變成iPS細(xì)胞的障礙物的性質(zhì)尚不清楚,，同時我們也不知道是否能讓iPS細(xì)胞重新編程變得具有確定性和高效率?，F(xiàn)在，Jacob Hanna及其同事發(fā)現(xiàn),，高效轉(zhuǎn)換是可能的,。他們發(fā)現(xiàn)，將2i/LIF生長條件和OSKM過度表達(dá)相結(jié)合,，再加上使Mbd3/NuRD co-repressor中和,，向多能性的確定性的、同步的重新編程就會出現(xiàn),。僅僅經(jīng)過7天時間的OSKM誘導(dǎo),，幾乎100%的小鼠和人類體細(xì)胞就轉(zhuǎn)變成了初始的iPS細(xì)胞。(生物谷Bioon.com)
生物谷推薦英文摘要
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.
