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【分享】全基因组RNA扫描揭示人类胚胎干细胞的决定因素 已有1人参与
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A genome-wide RNAiscreen reveals determinants of human embryonic stem cell identity 全基因组RNA扫描揭示人类胚胎干细胞的决定因素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. 由人类囊胚层衍生来的人类胚胎干细胞代表了干细胞生物学的一个里程碑。为了揭示hESC在科研和临床应用中的潜能，需了解能够决定hESC特性的遗传网络。 本文提出了全基因组RNAi扫描来识别在hESC中调控自我更新和多能性的基因。结果发现参与转录调控和染色质重组的一些功能不同的复合物。 本文揭示了转录因子PRDM14在调控多能性中的作用机制。PRDM14通过其临近增强子CR2，调控关键多能性基因POU5F1的表达。此外，PRDM14与其它关键TF（OCT4, NANOG, SOX2）共定位，说明PRDM14参与干细胞多能性的核心调控网络。功能获得实验中，发现当PRDM14与OCT4, SOX2和KLF4联合时能够增强人类成纤维细胞重编程效能。 本文发现一个新的hESC调控子PRDM14，作为一个重要的调控因子，对于维护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. 更多资料请查看www.bioknow.cn |
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