Synergistic transcriptional and post-transcriptional regulation of ESC characteristics by core pluripotency transcription factors in protein-protein interaction networks.
Synergistic transcriptional and post-transcriptional regulation of ESC characteristics by core pluripotency transcription factors in protein-protein interaction networks.
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DOI：
10.1371/journal.pone.0105180
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hua J
中科院分区：
文献类型：
--
作者：
Li L;Zhang L;Liu G;Feng R;Jiang Y;Yang L;Zhang S;Liao M;Hua J
维持胚胎干细胞（ESC）多能性的分子机制尚未得到很好的理解，但可能反映在复杂的生物网络中。然而，从计算系统生物学的角度对胚胎干细胞发育过程中转录和转录后调控的作用进行研究的还很少。在这项研究中，我们分析了蛋白质-蛋白质相互作用网络（PPINs）中的“核心”多能性转录因子（TF）OCT 4，SOX 2和NANOG的拓扑性质。此外，我们确定了在ESC发育过程中这些TF和PPIN中的microRNA（miRNA）之间的协同相互作用。结果表明，TF-靶点与非TF-靶点的PPIN在中心性特征上存在显著差异。我们还发现，存在多个“核心”多能性TF的一致调节。基于最短路径长度的分析，我们发现模块特性不仅在由共同或多个“核心”多能性TF调控的靶标内，而且在由不同TF调控的靶标组之间。最后，我们确定了这些TF和miRNA的协同调节。总之，在人和小鼠PPIN中使用计算方法分析“核心”多能性TF和miRNA的协同效应。
The molecular mechanism that maintains the pluripotency of embryonic stem cells (ESCs) is not well understood but may be reflected in complex biological networks. However, there have been few studies on the effects of transcriptional and post-transcriptional regulation during the development of ESCs from the perspective of computational systems biology. In this study, we analyzed the topological properties of the “core” pluripotency transcription factors (TFs) OCT4, SOX2 and NANOG in protein-protein interaction networks (PPINs). Further, we identified synergistic interactions between these TFs and microRNAs (miRNAs) in PPINs during ESC development. Results show that there were significant differences in centrality characters between TF-targets and non-TF-targets in PPINs. We also found that there was consistent regulation of multiple “core” pluripotency TFs. Based on the analysis of shortest path length, we found that the module properties were not only within the targets regulated by common or multiple “core” pluripotency TFs but also between the groups of targets regulated by different TFs. Finally, we identified synergistic regulation of these TFs and miRNAs. In summary, the synergistic effects of “core” pluripotency TFs and miRNAs were analyzed using computational methods in both human and mouse PPINs.
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影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
10.5
作者：
Cole, Megan F.;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.5
作者：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR
影响因子：
10.5
作者：
Avilion, AA;Nicolis, SK;Lovell-Badge, R
通讯作者：
Lovell-Badge, R
影响因子：
30.8
作者：
Ben-Porath, Ittai;Thomson, Matthew W.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.