These results indicate that there are both the complex interactions between different “core” pluripotency TFs during ESC development within transcriptional levels and the interactions occur across both transcriptional and posttranscriptional levels in biological networks. In this study, we globally analyzed the topological properties of targets of the “core” pluripotency TFs in PPINs, including OCT4, SOX2 and NANOG. In addition, the post-transciptional effects of miRNAs on these TFs were also analyzed in both human and mouse. Up to ten topological properties were included in the analysis process, including Shortest Path Length, Betweeness, Closeness, Cluster Coefficient, Degree, Eccentricity, Neighborhood Connectivity, Radiality, Stress and Topological Coefficient. All the above analyses were processed in three protein-protein interaction datasets, two miRNA target datasets and two species. Though there were different dataset scales of the three “core” TF targets between different databases and species, the common characteristic of these three “core” TFs in biological networks were still observed in our research. The use of several data sources and measurements in this study ensures the robust nature of the results obtained. Besides, all the above analysis was based on ESCs datasets. Consider the similar property of “stemness” with ESCs in many other types of stem cells, especially induced pluripotent stem cells, we infer that these three “core” TFs will have similar roles and characteristics in biological networks. With the increasing of high throughput datasets about targets of the “core” pluripotency TFs in other types of stem cells, similar research should be processed and compared with current results. We found significant differences in centrality properties between “core” pluripotency TF-targets and non-TF-targets in PPINs. These results were widespread in HPRD, human BioGRID and mouse BioGRID datasets. The numbers of centrality properties were 6 and 8 in human and mouse respectively. The former contained ASPL, BC, Degree, Eccentricity, Radiality and Stress, while the latter comprised ASPL, BC, Closeness, Degree, NC, Radiality, Stress and TC. Comparing the two results, we found that ASPL, BC, Degree, Radiality and Stress were robust and only CC among the 10 measurements could not be detected, which is used to judge the close link of node neighborhoods in biological networks. The reason why CC did not appear in the analysis was not clear. It may be because the targets of “core” pluripotency TFs perform their functions in relative isolation which may help to avoid harm to the complex environment in vivo during the development of ESCs. With the higher PF-2341066 central properties, these results indicate that targets of these three “core” TFs play more important roles than random genes during the development of ESCs. We found synergistic regulation of multiple “core” pluripotency TFs during the development of ESCs. As we hypothesized, no difference in topological properties was found between 1TFtargets, 2TF-targets and 3TF-targets in human PPINs, including HPRD and human BioGRID. The same tendency was also found in mouse PPINs from BioGRID.