Reprogramed somatic cells into pluripotent cells using a combination of seven small-molecule compounds and called them CiPS

Epigenetic modifications have also been found to play important roles in the maintenance of ‘stemness’. These results indicate that in addition to the genetic factors affecting the maintenance of pluripotency, complex epigenetic factors are also 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. According to previous studies, a small set of TFs, including OCT4, SOX2 and NANOG comprise the “core” pluripotency factors in ESCs. OCT4 has long been considered to play essential roles in maintaining pluripotency in vivo and in vitro. In fact, the concentration of OCT4 is crucial for pluripotency: reduced expression evokes trophoectoderm development, whereas enhanced expression leads to primitive endoderm differentiation. As a transcriptional partner of OCT4, SOX2 assembles on regulatory elements of target genes together with OCT4 to collaborate in transcriptional control, without directly interacting with OCT4 protein. The function of NANOG is to SP600125 129-56-6 promote the self-renewal of ESCs and alleviate the requirement for Leukemia Inhibitory Factor. Among OCT4 targets, about half are associated with SOX2. Furthermore, more than 90% of the target genes shared by OCT4 and SOX2 are also associated with NANOG. Based on the above results, some researchers have constructed biological networks that involve these TFs, and analyzed their properties during the development of ESCs. In a word, as key factors in the maintenance of the pluripotency and self-renewal of ESCs, OCT4, SOX2 and NANOG coordinate the regulation of downstream genes. Besides the traditional genetic impacts on the maintenance of ESC pluripotency, epigenetic regulation is also involved in the process of ESC development. In particular, more and more studies have found that miRNAs play important roles during the development of ESCs. miRNAs are endogenous single strand non-coding RNAs which can inhibit target mRNA expression in a post-transcriptional manner. It is characteristic of miRNAs that they regulate target genes in a minor manner and show temporal and spatial specificity. They may form a complex interaction network with other biological molecules in vivo. However it is not clear how the target genes of “core” pluripotency TFs regulate ESC development synergistically with miRNAs. In this study, we identified protein-protein interaction networks and analyzed the topological properties of the target genes of OCT4, SOX2 and NANOG in human and mouse ESCs. Further, we explored the effects of miRNAs on the posttranscriptional regulation of the target genes of these three “core” pluripotency TFs. We found that the centrality of “core” pluripotency transcription factor target genes is higher than that of randomly selected genes in PPINs. Furthermore, when genes are regulated by more “core” pluripotency TFs, they show more properties of centrality. The target genes regulated by both transcriptional and post-transcriptional methods also have higher centralit.