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Modern genome-wide genetic approaches to reveal intrinsic properties of stem cells.

机译:现代全基因组遗传方法揭示干细胞的内在特性。

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PURPOSE OF REVIEW: The clinical use of hematopoietic stem cells, which produce all mature blood cell lineages in the circulation, is continuously increasing. Identification of genes and gene networks specifying either stemness or commitment will not only be of major relevance for a fundamental understanding of developmental biology, but also for the emerging fields of tissue engineering and regenerative medicine. Our appreciation of the transcriptional machinery that distinguishes stem cells from their nonstem cell progeny is, however, rudimentary. State-of-the art genome-wide tools are now becoming available to elucidate intrinsic properties of stem cells. Here, we review recent progress that has been made in this field. RECENT FINDINGS: Approaches to study stem cell-specific genes and gene networks include genetical genomics, mRNA and microRNA expression profiling of carefully selected cells, proteomics, chromatin studies using 'CHIP-on-chip' tools, genome-wide binding site analyses for transcriptionfactors and chromatin-remodeling proteins, and tools to study the three-dimensional organization of gene loci. It is promising to see that the combined application of these tools has resulted in the identification of multiple novel genes that regulate stem cell self-renewal. SUMMARY: Exploitation of the available technology and integrating the data by translation into a dynamic model of networks, operating in all four dimensions, will be essential to fully comprehend the elusive concept of 'stemness'. It is time to harvest.
机译:审查目的:在循环中产生所有成熟血细胞谱系的造血干细胞的临床应用正在不断增加。确定干性或承诺性的基因和基因网络的鉴定,不仅对发育生物学的基本理解具有重要意义,而且对组织工程和再生医学的新兴领域也具有重要意义。然而,我们对区分干细胞和非干细胞后代的转录机制的认识是基本的。现在,可以使用先进的全基因组工具来阐明干细胞的内在特性。在这里,我们回顾了该领域的最新进展。最近的发现:研究干细胞特异性基因和基因网络的方法包括遗传基因组学,精心挑选的细胞的mRNA和microRNA表达谱分析,蛋白质组学,使用“芯片上芯片”工具进行的染色质研究,转录因子的全基因组结合位点分析和染色质重塑蛋白,以及研究基因位点的三维组织的工具。很有希望看到这些工具的组合应用已导致鉴定出调节干细胞自我更新的多个新基因。简介:利用现有技术并通过转换将数据集成到一个动态的网络模型中(在所有四个维度上运行),对于充分理解难以理解的“干性”概念至关重要。现在是时候收获了。

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