來(lái)自新加坡基因組研究所(GIS)和細(xì)胞和分子生物學(xué)研究所(IMCB)的科學(xué)家發(fā)現(xiàn)了人類干細(xì)胞“百變”的秘密,,而且只要啟動(dòng)這個(gè)被稱為PRDM14的基因,,任何普通細(xì)胞都有可能“變身”為干細(xì)胞,,成功率比現(xiàn)有技術(shù)高三倍。該研究發(fā)表于10月17日的Nature雜志上,。
擁有多能性(pluripotency)的胚胎干細(xì)胞(embryonic stem cell),,能變成人體里200多種細(xì)胞中的任何一種,自我“繁殖”能力也強(qiáng),,因此一直被視為各種絕癥的希望,。不過(guò),由于牽涉道德問(wèn)題,,胚胎干細(xì)胞研究一再受阻,,科學(xué)家只好另覓良方,。
科學(xué)人員近年就開(kāi)始鉆研“培育”多能性干細(xì)胞的可能性,通過(guò)重編程(re-programme)改變細(xì)胞基因,,讓普通細(xì)胞也具多能性,。由19名本地科學(xué)家組成的研究小組就花了三年,從2萬(wàn)1000組基因中,,找到了干細(xì)胞“多能性”的重要鑰匙,。
據(jù)稱這是有史至今,最大規(guī)模的干細(xì)胞基因研究,。
干細(xì)胞專題
2010年干細(xì)胞技術(shù)與應(yīng)用講座
干細(xì)胞發(fā)展編年史
全球五大干細(xì)胞治療中心
解讀干細(xì)胞臨床應(yīng)用標(biāo)準(zhǔn)與規(guī)則
干細(xì)胞之春——生物谷盤點(diǎn)2009
華夏干細(xì)胞產(chǎn)業(yè)技術(shù)創(chuàng)新戰(zhàn)略聯(lián)盟正式成立
參與研究的新加坡基因組研究院高級(jí)研究小組組長(zhǎng)黃學(xué)暉博士受訪時(shí)指出,,要讓普通細(xì)胞具多能性,需啟動(dòng)的基因有好幾組,,PRDM14只是其中之一,,但它卻也扮演著重要角色。
小組發(fā)現(xiàn),,在改造細(xì)胞時(shí)如果為細(xì)胞“添置”PRDM14基因組,,那最終培育出具多能性的細(xì)胞,將比平日多出三倍,。
此外,,他們也發(fā)現(xiàn)PRDM14只在人類的干細(xì)胞中扮演重要角色,對(duì)老鼠干細(xì)胞則不重要,。這顯示了不同物種間干細(xì)胞的差異,也再次彰顯了以人類細(xì)胞進(jìn)行研究的重要性,。
黃博士說(shuō):“在此之前,,研究員對(duì)人類胚胎干細(xì)胞的基因組合認(rèn)識(shí)很少,多數(shù)試驗(yàn)室都專注用老鼠細(xì)胞進(jìn)行研究,。但了解人類干細(xì)胞其實(shí)很重要,,如果不了解,我們又怎能研發(fā)新的科技,。”
不過(guò)黃博士坦誠(chéng),,目前還不清楚這項(xiàng)發(fā)現(xiàn)能如何應(yīng)用于醫(yī)藥治療。“除了PRDM14,,我們目前還在研究很多其他的基因組,。當(dāng)中一些可能對(duì)個(gè)別病癥具重要功能。”
“目前我們很難推算出一個(gè)時(shí)間表,,正如很多重要的治療,,從發(fā)現(xiàn)到最終的臨床應(yīng)用是需要時(shí)間的。”
雖有人擔(dān)心,,重新編排細(xì)胞基因可能會(huì)啟動(dòng)不良副作用,,但黃博士認(rèn)為,,隨著更多關(guān)鍵基因獲辨識(shí),重新編排細(xì)胞基因的方式也將更完善,。
黃博士表示,,目前一些常見(jiàn)的干細(xì)胞療法用的都是他人捐贈(zèng)的干細(xì)胞,可是新的研究卻能直接用病人本身的細(xì)胞“培育”出干細(xì)胞,,仿佛是為病人“量身”制定,,相信會(huì)更理想。
接下來(lái),,研究小組將繼續(xù)探討如何更好地為普通細(xì)胞“添置”PRDM14基因,,以及如何利用基因?qū)W科技“指引”干細(xì)胞“變身”成為個(gè)別種類的細(xì)胞。(生物谷Bioon.com)
生物谷推薦英文摘要:
Nature advance online publication 17 October 2010 | doi:10.1038/nature09531
A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
Na-Yu Chia1,2,10, Yun-Shen Chan1,3,10, Bo Feng1,10, Xinyi Lu1,4, Yuriy L. Orlov5, Dimitri Moreau6, Pankaj Kumar6, Lin Yang1, Jianming Jiang1, Mei-Sheng Lau1, Mikael Huss5, Boon-Seng Soh7, Petra Kraus7, Pin Li7, Thomas Lufkin7, Bing Lim7,8, Neil D. Clarke5,9, Frederic Bard6,9 & Huck-Hui Ng1,2,3,4,9
The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology1. The full potential of hESCs in research and clinical applications requires a detailed understanding of the genetic network that governs the unique properties of hESCs. Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs. Interestingly, functionally distinct complexes involved in transcriptional regulation and chromatin remodelling are among the factors identified in the screen. To understand the roles of these potential regulators of hESCs, we studied transcription factor PRDM14 to gain new insights into its functional roles in the regulation of pluripotency. We showed that PRDM14 regulates directly the expression of key pluripotency gene POU5F1 through its proximal enhancer. Genome-wide location profiling experiments revealed that PRDM14 colocalized extensively with other key transcription factors such as OCT4, NANOG and SOX2, indicating that PRDM14 is integrated into the core transcriptional regulatory network. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Altogether, our study uncovers a wealth of novel hESC regulators wherein PRDM14 exemplifies a key transcription factor required for the maintenance of hESC identity and the reacquisition of pluripotency in human somatic cells.
1Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672
2School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
3Graduate School for Integrative Sciences & Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456
4Dept of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543
5Computational and Systems Biology group, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672
6Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
7Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672
8Center for Life Sciences, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02115, USA
9Department of Biochemistry, National University of Singapore, 8 Medical Drive, Yong Loo Lin School of Medicine, Singapore 117597
10These authors contributed equally to this work.