2011年2月8日，北京生命科學(xué)研究所高紹榮實(shí)驗(yàn)室在Stem Cells 雜志在線發(fā)表文章,，首次報(bào)道了一個(gè)轉(zhuǎn)錄因子Oct4可以將滋養(yǎng)外胚層來源的滋養(yǎng)層干細(xì)胞重編程為具有分化為三胚層能力的多潛能干細(xì)胞,。
滋養(yǎng)層干細(xì)胞（TS）和胚胎干細(xì)胞（ES）是從哺乳動(dòng)物早期囊胚建立的兩類干細(xì)胞,，但是兩種干細(xì)胞具有巨大的差異，首先滋養(yǎng)層干細(xì)胞來源于屬于胚外組織的滋養(yǎng)外胚層細(xì)胞,，而胚胎干細(xì)胞則來源于將來分化為原始內(nèi)胚層和三胚層結(jié)構(gòu)的內(nèi)細(xì)胞團(tuán)細(xì)胞,。其次滋養(yǎng)層干細(xì)胞體內(nèi)體外只能分化為胎盤細(xì)胞，而胚胎干細(xì)胞卻可以分化為三胚層細(xì)胞,。滋養(yǎng)層干細(xì)胞是否可以重編程（或轉(zhuǎn)分化）為具有分化為三胚層能力的類胚胎干細(xì)胞還不清楚,。高紹榮實(shí)驗(yàn)室博士生吳彤首先從不同品系小鼠建立了數(shù)株滋養(yǎng)層干細(xì)胞，并且經(jīng)過體內(nèi)體外分化實(shí)驗(yàn)鑒定了所建滋養(yǎng)層干細(xì)胞的分化潛能,，即只能分化為胎盤細(xì)胞,。進(jìn)一步經(jīng)過基因表達(dá)分析發(fā)現(xiàn)滋養(yǎng)層干細(xì)胞本身表達(dá)諸如Sox2，c-Myc基因,，但是不表達(dá)Oct4,，Klf4基因；進(jìn)一步分析發(fā)現(xiàn)滋養(yǎng)層干細(xì)胞表達(dá)Esrrb基因,，因?yàn)榻谝黄芯空撐淖C明Esrrb基因可以取代Klf4基因重編程成纖維細(xì)胞為iPS細(xì)胞,，所以他們想是否可以利用少的因子甚至一個(gè)轉(zhuǎn)錄因子將滋養(yǎng)層干細(xì)胞轉(zhuǎn)變?yōu)槎酀撃芨杉?xì)胞。他們利用Tet-on可誘導(dǎo)系統(tǒng)將不同的基因組合轉(zhuǎn)入滋養(yǎng)層干細(xì)胞,，最終證明一個(gè)轉(zhuǎn)錄因子Oct4就可以將滋養(yǎng)層干細(xì)胞重編程為類似于胚胎干細(xì)胞的多潛能干細(xì)胞,，其間許多重要的表觀遺傳重編程事件諸如X染色體重新激活（X-chromosome reactivation），多能性基因啟動(dòng)子區(qū)DNA去甲基化等都在細(xì)胞命運(yùn)轉(zhuǎn)變過程中發(fā)生,，誘導(dǎo)形成的多潛能干細(xì)胞可以在體內(nèi)外分化為三胚層結(jié)構(gòu)的細(xì)胞類型,，并且可以高效的產(chǎn)生具有生殖系傳遞能力的嵌合體小鼠。
滋養(yǎng)層干細(xì)胞是繼神經(jīng)干細(xì)胞之后第二類干細(xì)胞可以由一個(gè)轉(zhuǎn)錄因子Oct4（在不添加其它小分子抑制劑情況下）轉(zhuǎn)變?yōu)槎酀撃芨杉?xì)胞,，同時(shí)該研究也為進(jìn)一步深入研究早期胚胎分化,，細(xì)胞命運(yùn)決定提供了重要的理論依據(jù)和研究思路。
我所與中國農(nóng)業(yè)大學(xué)聯(lián)合培養(yǎng)的博士研究生吳彤為本文的第一作者,。博士生王海濤,，何靜，康嵐,，蔣永華,，劉金超均參與了本研究。技術(shù)員張郁,，寇朝暉和蘭州大學(xué)第一附院的柳利軍,，張學(xué)紅大夫提供了重要的技術(shù)支持。高紹榮博士為該論文的通訊作者,。該研究由科技部和北京市科委資助,，在北京生命科學(xué)研究所完成,。（生物谷Bioon.com）
生物谷推薦原文出處：
Stem Cells DOI: 10.1002/stem.617
Reprogramming of Trophoblast Stem Cells into Pluripotent Stem Cells by Oct4
Tong Wu1,2, Haitao Wang2, Jing He2, Lan Kang2, Yonghua Jiang2, Jinchao Liu2, Yu Zhang2, Zhaohui Kou2, Lijun Liu3, Xuehong Zhang3, Shaorong Gao2
Keywords:Trophoblast stem cells;Pluripotent stem cells;Reprogramming;Cell fate conversion
Abstract
Embryonic stem (ES) cells and trophoblast stem (TS) cells are both derived from early embryos, yet these cells have distinct differentiation properties. ES cells can differentiate into all three germ layer cell types, whereas TS cells can only differentiate into placental cells. It has not been determined whether TS cells can be converted into ES-like pluripotent stem (PS) cells. Here we report that overexpression of a single transcription factor, Oct4, in TS cells is sufficient to reprogram TS cells into a pluripotent state. These Oct4 induced pluripotent stem (OiPS) cells have the epigenetic characteristics of ES cells, including X chromosome reactivation, elevated H3K27 me3 modifications and hypomethylation of promoter regions in Oct4 and Nanog genes. Meanwhile, methylation of promoter region in the Elf5 gene occurred during reprogramming of TS cells. The gene expression profile of OiPS cells was very similar to ES cells. Moreover, OiPS cells can differentiate into the three germ layer cell types in vitro and in vivo. More importantly, chimeric mice with germline transmission could be efficiently produced from OiPS cells. Our results demonstrate that one single transcription factor, Oct4, could reprogram the non-embryonic TS cells into pluripotent stem cells.
