Epigenetic regulation mechanisms in stem cell differentiation

Abstract

Pluripotent stem cells have the capability of differentiating into cells from all three germ layers endoderm, mesoderm and ectoderm; as well as an unlimited potency to self-renew, maintaining their stem cell identity. Embryonic stem cells that are derived from the inner cell mass of the mammalian blastocyst can give rise to a fully developed viable embryo with more than 200 different cell types, which essentially share the same genetic information, namely the DNA. The establishment of distinct cellular identities requires differential interpretation of this genetic information in the form of differential gene expression patterns, which is largely influenced by DNA accessibility and is modulated by mechanisms that are beyond DNA sequence, indicating epigenetic regulation. In eukaryotes, DNA is compacted into a macromolecular structure called chromatin. The packaging of DNA into chromatin is done in a dynamic manner so that the DNA can still be accessible to carry out cellular functions such as replication, transcription and DNA repair. The naked DNA first gets wrapped around the histone octamer containing two copies of each core histone H2A, H2B, H3 and H4, which constitutes the first step of compaction called the “beads on a string” conformation.1 Next, the linker histone H1 binds to the nucleosome at the DNA entry-exit point and further condenses the DNA into 30nm chromatin fiber. Metaphase chromosomes represent the most compact form of chromatin2