Abstract
Owing to their potential for differentiation into multiple cell types, multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine. The requirements for cellular differentiation of an adult stem cell are a loss of proliferation potential and a gain of cell-type identity. These processes could be restricted by epigenetic modifications that prevent the risks of lineage-unrelated gene expression or the undifferentiated features of stem cells in adult somatic cells. In this review, we focus on the role of DNA methylation in controlling the transcriptional activity of genes important for self-renewal, the dynamism of CpG methylation of tissue-specific genes during several differentiation programs, and whether the multilineage potential of adult stem cells could be imposed early in the original precursor stem cells through CpG methylation. Additionally, we draw attention to the role of DNA methylation in adult stem cell differentiation by reviewing the reports on spontaneous differentiation after treatment with demethylating agents and by considering the evidence provided by reprogramming of somatic cells into undifferentiated cells (that is, somatic nuclear transfer or generation of induced pluripotent cells). It is clear from the evidence that DNA methylation is necessary for controlling stem cell proliferation and differentiation, but their exact contribution in each lineage program is still unclear. As a consequence, in a clinical setting, caution should be exerted before employing adult stem cells or their derivatives in regenerative medicine and appropriate tests should be applied to ensure the integrity of the genome and epigenome.
Highlights
Multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine and have been identified in many organs and tissues, including bone marrow, peripheral blood, fat, skeletal muscle, brain, skin, cornea, heart, gut, liver, ovarian epithelium, and testis
Concluding remarks It is clear that cell differentiation of multipotent stem cells is a result of a complex and dynamic network of transcriptional regulators, among them epigenetic factors that play a central role through controlling the expression/ repression of tissue-specific genes and multipotencyrelated genes
Epigenetic treatments may have a pleiotropic effect on the differentiation of stem cells, depending on multiple factors, mainly the origin of the precursor cell and environment conditions [39,41,45], suggesting that global epigenetic modifications, though necessary, are not sufficient to transdifferentiate by themselves [46]
Summary
Multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine and have been identified in many organs and tissues, including bone marrow, peripheral blood, fat, skeletal muscle, brain, skin, cornea, heart, gut, liver, ovarian epithelium, and testis. Gene expression potential in stem cell renewal and differentiation could be regulated by epigenetic processes that confer a specific chromatin conformation of the genome, of which DNA methylation is the best characterized (Figure 1) [2]. DNA methylation, the addition of a methyl group to the carbon 5 of the cytosine into CpG contexts, is known to be an essential process in development and cellular differentiation [3]. It is involved in gene regulation of housekeeping and tissue-type genes, silencing of one allele of imprinted genes, and compensation of the extra copy of the X chromosome in females.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
