Abstract

The first differentiation event at the blastocyst stage in early mammalian development results in two distinct cell populations: the inner mass, which harbours embryonic stem cells (ESCs) and gives rise to the embryo, and the trophectoderm, which includes trophoblast stem cells (TSCs) and gives rise to the placenta and other extraembryonic tissues. This lineage potency restriction is set by various proteins, including epigenetic modifiers, which function by chemically modifying the DNA to regulate the expression of genes and, in turn, the proteins they encode. Tet enzymes are one such class of epigenetic modifiers. They catalyse the conversion of one epigenetic feature; 5-methylcytosine (5mC), to another; 5-hydroxymethylcytosine (5hmC). The Tet enzymes are known to be involved in the maintenance of the pluripotent state in ESCs. Our hypothesis is that they also play a role in safeguarding the developmental plasticity of TSCs. Understanding how the chemical modification of DNA (epigenetics) affects trophoblast differentiation paves the way for underpinning the mechanisms of placental development and disease.