Division of Stem Cell Research
Department of Trophoblast Research

The placenta is essential for normal mammalian development, and its abnormalities can cause various pregnancy complications. Despite its importance, our current knowledge of human placental development is very limited compared to other organs. Our lab is keen to understand the function and development of the human placenta. Using stem cell technologies we have developed, we are trying to recapitulate human placental development in vitro and understand the underlying mechanisms. We hope to make use of the obtained knowledge to improve artificial reproductive technologies and develop new treatments for pregnancy complications.



We are looking for students interested in placental development, disease, and evolution. Our lab encourages students to find important questions, observe the subject carefully, and publish papers. The lab staff will make every effort to support this process.  If you are interested in our research, please contact us.


1.Recapitulation and understanding of human implantation

It is widely accepted that the interaction between trophoblast and endometrial cells is the key to the successful implantation of the human embryo (Fig. 1).



However, the underlying mechanisms are not well understood. Our lab has developed a technique to derive human trophoblast stem cells (hTSCs) and revealed that these cells have similar properties to peri-implantation trophoblast cells (Fig. 2) (Okae et al. Cell Stem Cell 2018). 



We are also trying to generate an organoid model that recapitulates human endometrial tissue. In this project, we will develop a co-culture system of hTSCs and the human endometrial organoid model to elucidate the mechanisms of human implantation.


2.Development of new treatments for pregnancy complications

Placental abnormalities can cause pregnancy complications such as preeclampsia and fetal growth restriction. However, it is still unclear why abnormalities in the placenta occur and how these abnormalities cause disease symptoms. We have developed techniques to derive disease-specific hTSCs and successfully reproduced some key aspects of pregnancy complications (Takahiashi et al. PNAS 2019 and unpublished data). We will use these techniques to develop new treatments for pregnancy complications (Fig. 3).



3.Investigation of the mechanisms underlying placental evolution

Mammals acquired the placenta more than 100 million years ago, which has prompted mammalian diversification. The placenta is one of the most recently acquired mammalian organs, and its morphology and gene expression are highly diversified among mammals. For example, we have shown that gene regulatory mechanisms are substantially different between mouse and human placentas (Hamada et al. AJHG 2016, Okae et al. PLoS Genet 2014).  In this project, we will compare TSCs established from various mammalian species to understand the molecular mechanisms underlying placental diversification (Fig. 4).