KU Leuven: The fuse box of embryonic development

Stem cell biologists unravel regulation of placental cells
In order for all cells to perform their function correctly, DNA regulation is necessary. This is an essential process, especially during pregnancy, because embryonic cells have to develop into all possible cell types in a human body. An international team of researchers from KU Leuven, Babraham Institute, Radboud University, UGent and IMBA discovered that the protein PRC2 plays an important role in determining the ultimate function of the embryonic cells. This human development research may help us better understand the early stages of pregnancies and potentially contribute to the search for the cause of early miscarriages. The results are published today in Nature Cell Biology .

Every human started existence as a sperm cell and an egg cell. Five or six days after fertilization we speak of the blastocyst stage, consisting of a rapidly dividing cluster of cells. In the cluster, an outer cell group – which will form the placenta – can be distinguished from an inner one, the final embryo. Which cells belong to which group is determined by a complex and critical process in which the smallest mistake can stop embryonic development.

For this research, professor Vincent Pasque from KU Leuven collaborated with an international team from Babraham Institute (UK), Radboud University (NL), UGent and IMBA (O). In the lab, they examined how embryonic cells are regulated using a cell model that mimics the blastocyst stage during the first week of pregnancy.

The human body is made up of hundreds of different cell types that perform a wide variety of functions in different tissues and organs. However, each of these cells has the same DNA. You can compare it as if every cell contains a fuse box with the same switches, but that – depending on the function – the desired switches are turned on/off. “The first choice that embryonic cells have to make is whether they will belong to the outer or inner layer of the blastocyst. After all, this determines whether they should form the placenta or become part of the final embryo,” says Professor Pasque. “Our results show that this choice is not as simple as previously assumed. After all, to turn on the placental switches at the right time, several hurdles have to be overcome.”

Study of embryonic development
Special stem cells were used to study the first days of embryonic development. These cells in the lab exhibit the same properties as the embryonic cells that make up the blastocyst during pregnancy. “Thanks to this cell model, it is possible to study how embryos are formed during the first days after fertilization”, says researcher Irene Talon of KU Leuven. “We learned from this that the PRC2 protein is an important factor in determining which part of the blastocyst a cell will belong to. If we suppressed PRC2, more placental cells were formed. This led to the conclusion that PRC2 is an important hurdle that must be overcome in order to form a functional placenta.”

“Thanks to this research, we understand embryonic development better and we know which links are important for the formation of the placenta. In the longer term, this insight can contribute to research into embryo implantation in the first days after fertilization and why it can also go wrong”, concludes Professor Pasque.