Research and Education

The germ cell lineage ensures the creation of new individuals, perpetuating/diversifying the genetic and epigenetic information across the generations. 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 healthy offspring. We have also shown that human induced pluripotent stem cells (hiPSCs) robustly generate human primordial germ cell-like cells (hPGCLCs). Furthermore, by investigating the development of a non-human primate model, cynomolgus monkeys, we have defined a developmental coordinate of pluripotency among mice, monkeys, and humans, and shown that the germ cell lineage in primates is specified in the nascent amnion, providing a pivotal insight into the biological relevance of the hPGCLC induction pathway. More recently, we have succeeded in differentiating hPGCLCs into human oogonia that undergo a proper epigenetic reprogramming and acquire an immediately precursory state for meiotic entry. We hope that these lines of research will lead to a better understanding of the mechanism for the transmission/diversification of genetic information, for the regulation of epigenetic information, and for the acquisition of totipotency, among mice, monkeys, and humans.

Establishment of a long-term in vitro expansion system for human primordial germ cell-like cells (PGCLCs).

ZGLP1 induces the oogenic fate in mice. Images show immunofluorescence staining of SYCP3 (yellow) and DDX4 (magenta) expression in E15.5 oocytes (left) and mouse primordial germ cell-like cells (PGCLCs) in vitro overexpressing ZGLP1 (right).

Recent Publications

1. Kojima, Y., Yamashiro, C., Murase, Y., Yabuta, Y., Okamoto, I., Iwatani, C., Tsuchiya, H., Nakaya, M., Tsukiyama, T., Nakamura, T., Yamamoto, T., and Saitou, M. GATA transcription factors, SOX17 and TFAP2C drive the human germ-cell specification program, Life Science Alliance, 4, e202000974, 2021.
2. Ohta, H., Yabuta, Y., Kurimoto, K., Nakamura, T., Murase, Y., Yamamoto, T., and Saitou, M. Cyclosporin A and FGF signaling support the proliferation/survival of mouse primordial germ cell-like cells in vitro, Biology of Reproduction, 104, 344-360, 2021.
3. Murase, Y., Yabuta, Y., Ohta, H., Yamashiro, C., Nakamura, T., Yamamoto, T., and Saitou, M. Long-term expansion with germline potential of human primordial germ cell-like cells in vitro, The EMBO Journal, 39, e104929, 2020.
4. Nagaoka, S. I., Nakaki, F., Miyauchi, H., Nosaka, Y., Ohta, H., Yabuta, Y., Kurimoto, K., Hayashi, K., Nakamura, T., Yamamoto T., and Saitou, M. (2020). ZGLP1 is a determinant for the oogenic fate in mice, Science, 367, eaaw4115, 2020.
5. Yamashiro, C., Sasaki, K., Yabuta, Y., Kojima, Y., Nakamura, T., Okamoto, I., Yokobayashi, S., Murase, Y., Ishikura, Y., Shirane, K., Sasaki, H., Yamamoto, T., and Saitou, M. Generation of human oogonia from induced pluripotent stem cells in vitro, Science, 362, 356-360, 2018.

Laboratory

Professor: Mitinori Saitou
Associate Professor: Hiroshi Ohta
Program Specific Associate Professor: Tomonori Nakamura
Program-Specific Senior Lecturer: Ikuhiro Okamoto
Program-Specific Senior Lecturer (CiRA): Shihori Yokobayashi
Assistant Professor: Masahiro Nagano
Assistant Professor: Ken Mizuta
Program Specific Assistant Professor: Yukihiro Yabuta

Tel: +81-75-753-4335
Fax: +81-75-751-7286
e-mail: saitou@anat2.med.kyoto-u.ac.jp