Dept. of Life Science Frontiers
Mitinori Saitou (Professor)
Mitinori Saitou M.D., Ph.D.
Procreation depends on the fusion of two germ cells, sperm and oocytes, which transfers genetic and epigenetic information of the parents to the offspring. We are investigating the mechanisms that determine the development of germ cells. These studies will also examine how aberrations in such mechanisms lead to diseases such as infertility and genetic abnormalities in offspring.
We have successfully generated primordial germ cell-like cells (PGCLC) in vitro from mouse ESCs and iPSCs. As the name suggests, these cells behave like primordial germ cells, which are responsible for producing sperm and oocytes. We confirmed that these cells contribute to the generation of healthy offspring. We have used our PGCLC as a model to investigate a number of key mechanisms for germ cell development, including the transcription and signaling regulators and the epigenome reprogramming mechanism. We have also established methods for the proliferation of PGCLCs and their differentiation to spermatogonial stem cells in vitro. Using mouse PGCLCs as our model, we are investigating oocyte development, meiosis, and the effects of sex chromosome abnormalities on fertility.
Based on these results, we developed a technology to induce human PGCLCs from human iPS cells. To further evolve the human germ cell in-vitro induction technology, we proceeded with research in cynomolgus monkeys, the most similar to humans of the primates suitable as experimental animals, and identified the developmental coordinates of the pluripotency spectrum in mice, monkeys, and humans, and traced the origin of primate germ cell lineages to the early-stage amniotic membrane. In parallel, we succeeded in inducing epigenetic reprogramming in human PGCLCs and differentiating them into early-stage egg cells through the oogonium stage. We also succeeded in the in vitro proliferation of humanPGCLCs to a one-million-fold level.
Based on these models, we aim to extend the study of human germ cell development.