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Principal Investigators

Dept. of Life Science Frontiers 
Mitinori Saitou (Professor)

Mitinori Saitou Photo
Research Overview

As most people know, 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 genetic and epigenetic mechanisms that determine the development of germ cells. These studies will also examine how aberrations in these mechanisms lead to related 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 determinants in germ cell development including the transcription and signaling factors responsible for their induction from PS cells and the epigenome reprogramming mechanism. We have also established methods for the proliferation of PGCLCs and their differentiation to spermatogonial stem cells in vitro. Finally, 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 primordial germ cell-like cells 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, identified the development 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. We further induced epigenetic reprogramming in human primordial germ cell-like cells and succeeded in inducing their differentiation into early-stage egg cells via the oogonium stage.

We aim to extend these primate projects to the study of human germ cell development.

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