FUNCTIONAL IMPACT OF EPIGENETIC MODIFICATIONS ON STEM CELL FATE DETERMINATION

Abstract

Stem cells are highly plastic similar to their ability to self-renew and develop into a variety of more specialized cell types, and thus they are the key to development, tissue homeostasis, and regenerative medicine. An accumulating body of evidence suggests that heritable yet reversible alterations that do not affect the DNA sequence, called epigenetic regulation, is a key to the process of stem cell fate determination. The combination of critical epigenetic events such as DNA methylation, histone alterations, chromatin remodeling or non-coding RNA-mediated regulation, orchestrate gene expression programs that result in pluripotency or lineage-specific differentiation of a stem cell. These processes work in a very dynamic and coordinated way, which provides a sufficient level of control over the transcriptional activity in terms of time and space. This review summarizes recent progress in the field of epigenetic landscape regulation of stem cell self-renewal and differentiation, the balance between activating and repressive states of the chromatin, the role of bivalent domains, and the effects of the epigenetic reprogramming in induced pluripotent stem cells. Moreover, non-coding RNAs integration into epigenetic networks has been argued to be a crucial level of regulatory complexity shaping cellular identity. The clinical utility of epigenetic regulation is becoming apparent and there is much promise in the regenerative therapies, disease modeling and the treatment of diseases that have aberrant epigenetic regulation, such as cancer where there is a disruption of normal stem cell activity. Although significant advances have been achieved, there are still issues with deciphering the complexity and context-dependence of the epigenetic regulation process. Future studies that incorporates multi-omics techniques and new powerful computational systems are likely to advance our knowledge and allow an accurate manipulation of stem cell fate to treat diseases. Altogether, epigenetic processes are inherent controllers of stem cell life, and potential actions in next-generation biomedical procedures.