Challenging the Elucidation of Placental Formation Mechanisms
With the rare exception of species such as the platypus, mammals form a placenta once the embryo (fertilized egg) implants in the uterus. The placenta enables fetal survival and growth by transferring oxygen and nutrients from the mother’s blood to the developing fetus until birth. This organ is composed of several specialized cell types, most of which belong to a group known as trophoblast cells, derived from the fertilized egg itself. This means the fetus creates the placenta—an organ essential for its own survival and growth. When the placenta fails to form properly or does not function as it should, fetal growth can be restricted, or the fetus may die before birth.
Our research uses Trophoblast Stem cells (TS cells), the cell lines established from mouse embryos. TS cells allow us to recapitulate the differentiation of trophoblast cells in vitro. This makes it easy to analyze at the genetic and protein level how a gene is regulated and functions during the differentiation process. Through this research, we hope to gain fundamental knowledge that will lead to a better understanding, prevention, and diagnosis of human pregnancy-related diseases.
Educational approach
Embrace the Unexpected
In recent years, our research has expanded to integrate RNA biology, led by Associate Professor Kataoka, with a focus on investigating the significance of alternative splicing in trophoblast stem (TS) cells. While students report their individual research progress to faculty members on a regular basis, we also hold laboratory-wide progress report sessions every two to three months. These rotating presentations allow all members to share updates, deepen their understanding of one another’s experiments, and exchange constructive feedback.
When results differ from predictions or expectations, we encourage students not to stop at “I don’t understand,” but instead to develop multiple hypotheses, design approaches to test them, and carry out those experiments. The “unexpected” is often the seed of new discovery. From a more personal perspective, I also value the motto “beauty lies in the details,” and therefore provide close guidance on the design of presentation slides, graphs, and other forms of research communication.
Our graduates pursue diverse career paths after completing their degrees. For example, in recent years, PhD alumni have gone on to positions such as a project assistant professor at a Japanese university, postdoctoral researcher in the United States, and technical sales specialist at an international company providing next-generation sequencing and bioinformatics services. Each graduate chooses a path that best matches their interests and skills.
Vision for industry-academia collaboration
Unlocking the Full Potential of TS Cells
In our recent studies, we conducted a screening of low-molecular-weight compounds that influence TS cell differentiation. We identified two compounds that suppress differentiation even under differentiation-inducing conditions, and one compound that promotes differentiation into a specific type of trophoblast cell (https://doi.org/10.1016/j.bbrc.2022.10.085). Although the mechanisms of action of these compounds remain unclear, elucidating them may contribute to the development of drugs that inhibit placental formation. In parallel, we have established culture conditions that enable three-dimensional growth of TS cells (https://doi.org/10.1262/jrd.2020-119). When differentiation is induced under these 3D conditions, cell aggregates form and show higher expression of marker genes for differentiated trophoblast cells compared with conventional 2D cultures, suggesting that the 3D system provides a more favorable environment for differentiation. Building on this technique, we aim to develop miniature placental organoids (“mini-placentas”) that recapitulate key features of placental formation.
We are seeking collaborators who are interested in advancing these studies and exploring their applications together.
