Metabolism is a major player in early human development
Human life begins with the fusion of an egg cell and a sperm cell. During the first cell divisions, the cells are all identical, but very soon they will have to make their first decision on which way to go. Either to become the embryo or placenta. New discoveries into this first decisive step of human life have been made and published in Nature Cell Biology by Associate Professor Jan Żylicz’s research group at the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW.
“We asked this really basic question of how a cell knows what it is and what to become” says Associate Professor Jan Żylicz. “And here we find a direct link between cell identity and how the cell produces and consumes energy, its metabolism.”
The researchers use human embryonic stem cells to model this early stage in development. In a petri dish it is possible to coax them towards a specific identity, and PhD student Karlien Van Nerum is an expert in generating placental cells. She also makes use of a rather new technique to form blastoid structures from the embryonic stem cells that resemble the human embryo at the blastocyst stage.
“This project is a perfect example of how different skills in the group synergized into something excellent. This has really been a team effort” says Karlien Van Nerum who is the first author of the research article.
In her stem cell model, Karlien and her colleagues detected that boosting metabolism helps the cells to become placental.
“A fun fact is that the discovery was made from what was supposed to be just a control experiment for a different project. It all started from this simple observation made by Karlien” says Associate Professor Jan Żylicz.
This study found that a specific molecule, α-ketoglutarate (αKG), is key. High αKG levels within the stem cells seem to help them become placental. Metabolism has previously been reported to improve functionality of specific tissues, but this is the first time that its role in early human development has been revealed. Improving placental cells could open new avenues for human IVF treatment advancement.
“Our clinical collaborators say that even incremental improvements in embryo quality, development or implantation success can provide substantial effects on the general population, given the large number of women undergoing treatment daily. Even an improvement of 5% will have a noticeable impact on the number of successful pregnancies.” says Associate Professor Jan Żylicz.