Embryonic Stem Cells (ESCs)
ESCs are obtained from the inner cell mass (ICM) of a blastocyst, which is an early-stage preimplantation embryo. In the human, embryos reach the blastocyst stage approximately 4–5 days post fertilization, at which time they consist of 50–150 cells. ESCs are distinguished by their ability to differentiate into any cell type and to propagate and their main properties include pluripotency (the ability of differentiate into tissues derived from all three germ layers), self-renewal (maintenance of an undifferentiated state) and limitless proliferative potential. As ESCs from the ICM are pluripotent they can form primitive ectoderm, which ultimately differentiates during gastrulation into all cell derivatives of the three primary germ layers-the ectoderm, endoderm and mesoderm. This includes differentiation into more than 220 cell types in the adult body. Pluripotency is a major trait that distinguishes ESCs from adult stem cells; whereas ESC can generate all cell types in the body, adult stem cells are multipotent and can only generate limited number of cell types. Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely in an undifferentiated state, allowing ESCs to be employed as useful tools for both research and regenerative medicine, as they can produce limitless numbers for ongoing research or clinical use.
Core networks of interconnected transcription factors (TF) control the ability of ESCs to maintain self-renewal or differentiate into lineages of all three germ layers. In coordination with these core networks, cell-fate transitions are determined by epigenetic mechanisms that facilitate histone modification and downstream chromatin events. These changes in chromatin are directly responsible for controlling DNA access, the availability of sequence signals and the recruitment of RNA Polymerase II (RPII). In mouse ESC (mESCs), the pluripotent state is controlled by a core group of interconnected genes, including targets of the Leukemia Inhibitory Factor (LIF) and BMP signaling pathways (Stat3 and Smad1 respectively), pluripotent and reprogramming factors (Oct4, Sox2, Klf4, Myc, Nanog), selfrenewal regulators (Esrrb, E2f1, Tcfcp2l1 and Zfx) and epigenetic mechanisms (Suz12 and Ctcf).