Understanding Embryonic Stem Cell Pluripotency Through Its Key Players

Certain transcription factors, cofactors, chromatin regulators are identified as the key players in establishing the embryonic stem cell ground state. The activation and silencing of genes in response to potency and lineage development act as the regulatory circuits. Insights into these regulatory circuitory have uncovered fundamental genetic and epigenetic mechanisms that control gene expressions to maintain the ground state. At one end of the circuit are the core transcription factors that self regulate their own gene expression. These factors further activate transcription of genes involved in pluripotency and contribute to the arrest of expression of lineage specific genes. The core transcription factors mediate binding of the enhancers with signaling factors there by extending the circuit to communicate the signals directly to the genes regulated by the core factors. The core factors also create an undifferentiated state through chromatin regulators that remodify the regulatory gene sequences of specific lineages to inactive states. Understanding the embryonic stem cell ground state in terms of its various regulatory aspects serves as both a baseline for understanding the changes that occur as cells differentiate and develop and as a means to understand the basic biology of these cells. It also helps in understanding the mechanisms behind induced pluripotent cells in vitro culture conditions that might contribute to stem cell based translational medicines.