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【分享】全基因組RNA掃描揭示人類胚胎干細(xì)胞的決定因素 已有1人參與
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A genome-wide RNAiscreen reveals determinants of human embryonic stem cell identity 全基因組RNA掃描揭示人類胚胎干細(xì)胞的決定因素Na-Yu Chia, Yun-ShenChan, Bo Feng, XinyiLu, YuriyL. Orlov, DimitriMoreau, and PankajKumar et al.Nature. 2010 Nov 11;468(7321):316-20. Epub2010 Oct 17. 由人類囊胚層衍生來的人類胚胎干細(xì)胞代表了干細(xì)胞生物學(xué)的一個(gè)里程碑。為了揭示hESC在科研和臨床應(yīng)用中的潛能，需了解能夠決定hESC特性的遺傳網(wǎng)絡(luò)。 本文提出了全基因組RNAi掃描來識(shí)別在hESC中調(diào)控自我更新和多能性的基因。結(jié)果發(fā)現(xiàn)參與轉(zhuǎn)錄調(diào)控和染色質(zhì)重組的一些功能不同的復(fù)合物。 本文揭示了轉(zhuǎn)錄因子PRDM14在調(diào)控多能性中的作用機(jī)制。PRDM14通過其臨近增強(qiáng)子CR2，調(diào)控關(guān)鍵多能性基因POU5F1的表達(dá)。此外，PRDM14與其它關(guān)鍵TF（OCT4, NANOG, SOX2）共定位，說明PRDM14參與干細(xì)胞多能性的核心調(diào)控網(wǎng)絡(luò)。功能獲得實(shí)驗(yàn)中，發(fā)現(xiàn)當(dāng)PRDM14與OCT4, SOX2和KLF4聯(lián)合時(shí)能夠增強(qiáng)人類成纖維細(xì)胞重編程效能。 本文發(fā)現(xiàn)一個(gè)新的hESC調(diào)控子PRDM14，作為一個(gè)重要的調(diào)控因子，對(duì)于維護(hù)hESC多能性及其重要。 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 geneswhich 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. 更多資料請(qǐng)查看www.bioknow.cn |
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holyala
木蟲 (著名寫手)
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- 專業(yè): 基因組學(xué)
2樓2010-12-06 18:05:57
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