Abstract
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.
Highlights
The capacity to differentiate into different cell types, a property known as pluripotency, is a defining property of embryonic stem cells (ESCs)
When we investigated the regulation of multiply ‘‘core’’ pluripotency transcription factors (TFs) during the development of ESCs in protein-protein interaction networks (PPINs), one question was triggered about whether there are closer relationships between targets of these TFs
From the Human Protein Reference Database (HPRD) and mouse Biological General Repository for Interaction Datasets (BioGRID) databases we found that the SPLs of three TFs were smaller than those of most other groups, but similar results were not observed in the PPIN of the human BioGRID
Summary
The capacity to differentiate into different cell types, a property known as pluripotency, is a defining property of embryonic stem cells (ESCs). Pluripotency may be conferred on somatic cells following their fusion with ESCs [3] During this process, the transcription factor (TF) NANOG is expressed, and this may facilitate fusion-induced pluripotency [4]. Epigenetic modifications (DNA methylation, histone modification, miRNAs and other methods of epigenetic regulation) have been found to play important roles in the maintenance of ‘stemness’ [11,12,13] These results indicate that in addition to the genetic factors affecting the maintenance of pluripotency, complex epigenetic factors are involved in the transformation of ESCs. In order to understand the mechanism by which pluripotency is established and maintained in ESCs, further effort will be required to research all aspects of the properties of molecules and their complex interactions in the biological networks which are involved in transcriptional and post-transcriptional regulation
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