Research Overview

Germ cells differentiate into sperm and egg cells (oocytes), the fusion of which creates a new individual. Understanding the mechanisms involved in the development of germ cells will give us a direct key to understanding the mechanisms of genetic information transmission and epigenetic control and thereby cast light on the mechanisms underlying infertility, hereditary disease, and epigenome abnormalities.

We have been investigating the mechanism for germ-cell development and have shown that mouse embryonic stem cells (mESCs)/induced pluripotent stem cells (miPSCs) are induced into primordial germ cell-like cells (mPGCLCs) with a robust capacity both for spermatogenesis and oogenesis and for contributing to offspring. These works have served as a basis for elucidating key mechanisms during germ-cell development such as epigenetic reprogramming, sex determination, meiotic entry, and nucleome programming.

By investigating the development of cynomolgus monkeys as a primate model, we have defined a developmental coordinate of pluripotency among mice, monkeys, and humans, identified the origin of the primate germ-cell lineage in the amnion, and have elucidated the X-chromosome dosage compensation program in primates. Accordingly, we have succeeded in inducing human iPSCs (hiPSCs) into human PGCLCs (hPGCLCs) and then into oogonia with appropriate epigenetic reprogramming. We have also shown that hPGCLCs can be propagated to ~106-fold over a period of 4 months under a defined condition. These studies have established a foundation for human in vitro gametogenesis.

Based on these models, we aim to extend the study of human germ cell development.