The response of murine embryonic fibroblast to abnormal expression of Yamanaka factors

Background and Aim: It remains unclear how the ectopic expression of defined transcription factors induces dynamic changes in gene expression profiles that establish a pluripotent state during direct cell reprogramming. Several reports have shown that reprogramming is a multistep process that includes accelerated cell proliferation, morphological changes of the cells, a mesenchymal-to-epithelial transition (MET), and unidentified stochastic events. Transcription factors often act in concert with cofactors and modifiers to turn the gene expression on or off. In a recent study microarrays related to expression of genes in mouse embryonic fibroblasts which were infected with vectors containing transcription factors Oct۴, Sox۲, Klf۴, c-Myc were published. its results were obtained in the form of a dataset and analyzed.Methods: A raw dataset has been extracted from GEO datasets (NCBI). In its heat map the genes which had the most difference in terms of expression were selected and they were subjected to furtheranalysis including protein associated networks in String-db. And also GEO۲R results were analyzed with String network package.Results: As it was previously determined, Transcription Factors are the means for regulation of gene expression. But the result, i.e. ۱۴۷ gene sets out of ۱۵۱۵, showed that there is a negative regulation on gene expression when the cells are exposed to Yamanaka factors. Moreover, ۱۱ gene sets out of ۴۴, are contributed to the inhibition of DNA methylation when Embryonic fibroblast is subjected to above-maintained factors. The results demonstrate that after several days, the expression of genes related to DNA repair system changes remarkably in embryonic fibroblasts which were infected with retroviruses. It is of great value to consider that also expression of genes related to pathways like “cellular response to DNA damage stimulus” had changed dramatically, since the cells were infected.There are also other genes in which their expression changes after infecting the cells with the above-mentioned vectors. These genes are somehow related to “histone demethylase activity (H۳-K۹ specific)” pathway and it shows that infecting cells with those viruses can result in epigenetic regulation of gene expression.Conclusion: The process of DNA demethylation and the activation of histone demethylase could be hallmark during the dedifferentiation. And also the results which were mentioned shows the metabolic pathways could be cooperating with DNA repair. As science improves in iPSC field, the demand toward knowing more about its mechanisms grows.

Keywords:

dedifferentiation