如果要使人類(lèi)胚胎干細(xì)胞在研究和臨床應(yīng)用中的全部潛力都發(fā)揮出來(lái)，我們便需要對(duì)掌控它們獨(dú)特性質(zhì)的遺傳網(wǎng)絡(luò)有一個(gè)細(xì)致的了解。
一項(xiàng)全基因組RNA干涉掃描,，在人類(lèi)胚胎干細(xì)胞中識(shí)別出自我更新和多能性的大量新調(diào)控因子,。例如,，PRDM14是維持人類(lèi)胚胎身份及體細(xì)胞向多能性重新編程所需的一個(gè)關(guān)鍵轉(zhuǎn)錄因子,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi:10.1038/nature09531
A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
Na-Yu Chia,Yun-Shen Chan,Bo Feng,Xinyi Lu,Yuriy L. Orlov,Dimitri Moreau,Pankaj Kumar,Lin Yang,Jianming Jiang,Mei-Sheng Lau,Mikael Huss,Boon-Seng Soh,Petra Kraus,Pin Li,Thomas Lufkin,Bing Lim,Neil D. Clarke,Frederic [email protected]& Huck-Hui Ng
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.
