دی متیلاسیون DNA و القای سلولهای بنیادی
Abstract
۱٫ Introduction
۲٫ DNA methylation and its role in cell fate decision
۳٫ Demethylation studies methods
۴٫ DNA demethylation and induction of stem cells
۵٫ Role of DNA demethylation in differentiation and transdifferentiation
۶٫ Controversy between transdifferentiation and dedifferentiation
۷٫ Effect of demethylation agents on in-vivo generation of stem cells
۸٫ Cancer Stem Cells and DNA methylation
۹٫ Conclusion
Disclosure of competing interest
Acknowledgments
References
Abstract
DNA methylation is an epigenetic factor, which plays important roles in embryo and many other diseases development. This factor determines gene expression, and when half of them have CpG islands, DNA methylation and its enzyme effectors have been under the vast studies. Whole genome DNA demethylation is a crucial step of embryogenesis and also cell fate determination in embryos. Therefore, demethylation agents were used as a tool for dedifferentiation and transdifferentiation. Although many of these efforts have been successful, but using this method gave us a vast spectral cell type which is confusing. In this article, we briefly reviewed DNA methylation, and its role in embryogenesis and gene expression. In addition to that, we introduce studies that used this action as a direct method in induction of stem cells and cell fate decision.
Introduction
It has been shown that, epigenetic factors determine transcriptome of cells. These factors determine cell functions and identities [1]. Cell fate determination is among the most significant aspects influenced by these factors [2]. DNA methylation occurring on cytosine in mammals is a major epigenetic factor, which its presence and absence may pose control over 50% of genes, especially developmental-related genes [3]. It has been hypothesized that; DNA demethylation is one of the most significant events in initiation of embryo development after fertilization, which has been named as Zygote Gene Activation (ZGA) [4]. This procedure induces expression of many stemness-related genes. Recently, many studies showed role of DNA demethylation and other epigenetic factors in changing cell fate [2]. It has been proved that, DNA demethylation could change fate of specific somatic cells to another somatic identity in a process named as transdifferentiation [5]. This phenomenon can reprogram somatic cells directly to stem cells [6]. DNA methylation enzyme effectors can establish new fates in differentiation process of stem cells as well [7]. Although it is believed that, disruption of epigenome or reactivation of developmental process in demethylation process could be a potential answer to these phenomena, but related findings have shown that, different roles of DNA demethylation are very confusing to determine. Furthermore, the basic concept and application of this field have been hindered because of its reproducibility and cell fate heterogeneity.