Derivation of an interaction/regulation network describing pluripotency in human.

Derivation of an interaction/regulation network describing pluripotency in human.
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描述人类多能性的相互作用/调节网络的推导

DOI:
10.1016/j.gene.2012.04.025
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发表时间:
2012
期刊:
影响因子:
3.5
通讯作者:
Fuellen G
Fuellen G
中科院分区:
生物学3区
文献类型:
--
作者:
Lustrek M;Singh NK;Fuellen G

文献摘要

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鉴定多能性的关键基因/蛋白及其相互关系是理解多能性的诱导和维持的重要步骤。实验方法在小鼠中积累了大量的相互作用/调控数据。我们调查多远,这些信息可以转移到人类,最感兴趣的物种,实验数据是有限的。为了解决这个问题,我们将现有的小鼠多能性网络(PluriNetWork)映射到人类。我们将基因/蛋白质之间的相互作用和调控联系从小鼠转移到人类的基础上的基因/蛋白质的正交关系(称为interlog映射)。为了减少假阳性的数量,我们使用了四种不同的方法:系统发育分析,基因本体语义相似性,基因共表达和RNA干扰(RNAi)数据。通过一种新的方法,使用有关已知参与多能性的基因的信息,从文献中评估的方法和由此产生的网络。RNAi方法被证明是过滤不可能的相互作用的最佳方法,因此它被用于构建最终的人类多能性网络。RNA干扰数据基于人类胚胎干细胞(hECs),通常认为这些细胞处于(启动的)外胚干细胞状态。因此,我们假设最终的人类网络可能更接近地反映了(致敏的)外胚层干细胞状态,而小鼠网络更接近地反映了(未致敏的/幼稚的)胚胎干细胞状态。
Identification of the key genes/proteins of pluripotency and their interrelationships is an important step in understanding the induction and maintenance of pluripotency. Experimental approaches have accumulated large amounts of interaction/regulation data in mouse. We investigate how far such information can be transferred to human, the species of maximum interest, for which experimental data are much more limited. To address this issue, we mapped an existing mouse pluripotency network (the PluriNetWork) to human. We transferred interaction and regulation links between genes/proteins from mouse to human on the basis of orthologous relationship of the genes/proteins (called interolog mapping). To reduce the number of false positives, we used four different methods: phylogenetic profiling, Gene Ontology semantic similarity, gene co-expression, and RNA interference (RNAi) data. The methods and the resulting networks were evaluated by a novel approach using the information about the genes known to be involved in pluripotency from the literature. The RNAi method proved best for filtering out unlikely interactions, so it was used to construct the final human pluripotency network. The RNAi data are based on human embryonic stem cells (hESCs) that are generally considered to be in a (primed) epiblast stem cell state. Therefore, we assume that the final human network may reflect the (primed) epiblast stem cell state more closely, while the mouse network reflects the (unprimed/naïve) embryonic stem cell state more closely.
DOI: 10.1126/science.287.5450.116
发表时间: 2000-01-07
期刊: SCIENCE
影响因子: 56.9
作者:
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发表时间: 2006
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发表时间: 2001-12-01
期刊: GENOME RESEARCH
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发表时间: 2010-03-31
期刊: STEM CELLS
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β-连环蛋白的局部减少有助于人类胚胎干细胞的分化。
DOI: --
发表时间: 2008
期刊: Biochemical and Biophysical Research Communications - BBRC
影响因子: --
作者:
H. Lam;S. Patel;Janelle Wong;J. Chu;A. Lau;Song Li
通讯作者: Song Li