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.

We have also generated PGCLCs from human iPSCs, having compared the induction efficiencies for germ lineage
between iPSC clones and found the molecular and signaling factors responsible for the different
efficiencies. Experiments with cynomolgus monkey iPSC-derived PGCLCs have allowed us to analyze germ lineage
development across different mammalian species and identify the early amniotic membrane as the origin of
germ cells in primates.

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

Members

Principal Investigator

Mitinori Saitou

Position: Professor
Laboratory Website: https://anat.cell.med.kyoto-u.ac.jp/index_en.html

Hiroshi Ohta

Associate Professor
Ikuhiro Okamoto

Junior Associate Professor
Shihori Yokobayashi

Junior Associate Professor
Ken Mizuta

Assistant Professor
Ayaka Kitamura

Program-Specific Researcher
Yusuke Murase

Program-Specific Researcher
Yoshiaki Nosaka

Program-Specific Researcher
Masanori Kawasaki

Program-Specific Researcher
Yumiko Nagai

Assistant Research Staff
Nae konishi

Assistant Research Staff
Marie Kawasaki

Assistant Research Staff
Erika Tsutsumi

Assistant Research Staff
Mieko Yoshida

Assistant Research Staff
Ryuta Yokogawa

D4
Hideki Matsuoka

D4
Hiromichi Sasada

D4
Hanbo Wang

D4
Xiaocong Liu

D4
Asami Ikeda

D3
Manami Mizuyama

D3
Shuto Deguchi

D2
Hiroto Kuma

D2
Akinaga Kusano

D2
Pimpitcha Puangsricharoen

D2
Fumiya Umemura

B5

Publications

Murase, Y., Yokogawa, R., Yabuta, Y., Nagano, M., Katou, Y., Mizuyama, M., Kitamura, A., Puangsricharoen, P., Yamashiro, C., Hu, B., Mizuta, K., Ogata, K., Ishihama, Y., and Saitou M. (2024) In vitro reconstitution of epigenetic reprogramming in the human germ line, Nature, DOI: https://doi.org/10.1038/s41586-024-07526-6

Mizuta K, Saitou M. Key mechanisms and in vitro reconstitution of fetal oocyte development in mammals. (2023) Curr Opin Genet Dev., 82:102091. DOI: 10.1016/j.gde.2023.102091

Gyobu-Motani S, Yabuta Y, Mizuta K, Katou Y, Okamoto I, Kawasaki M, Kitamura A, Tsukiyama T, Iwatani C, Tsuchiya　H, Tsujimura T, Yamamoto T, Nakamura T, Saitou M. Induction of fetal meiotic oocytes from embryonic stem cells in　cynomolgus monkeys. (2023) EMBO J., 42(9): e112962. DOI: 10.15252/embj.2022112962

Imoto Y, Nakamura T, Escolar EG, Yoshiwaki M, Kojima Y, Yabuta Y, Katou Y, Yamamoto T, Hiraoka Y, Saitou M. (2022) Resolution of the curse of dimensionality in single-cell RNA sequencing data analysis, Life Science Alliance, 9;5(12):e202201591. DOI: 10.26508/lsa.202201591

Mizuta K, Katou Y, Nakakita B, Kishine A, Nosaka Y, Saito S, Iwatani C, Tsuchiya H, Kawamoto I, Nakaya M, Tsukiyama　T, Nagano M, Kojima Y, Nakamura T, Yabuta Y, Horie A, Mandai M, Ohta H, Saitou M. Ex vivo reconstitution of fetal　Oocyte development in humans and cynomolgus monkeys. (2022) EMBO J., 41(18): e110815. DOI: 10.15252/embj.2022110815

Ishikura Y, Ohta H, Nagano M, Saitou M. Optimized protocol to derive germline stem-cell-like cells from mouse pluripotent stem cells. (2022) STAR Protoc., 3(3):101544. DOI: 10.1016/j.xpro.2022.101544

Nagano M, Hu B, Yokobayashi S, Yamamura A, Umemura F, Coradin M, Ohta H, Yabuta Y, Ishikura Y, Okamoto I,Ikeda　H,　Kawahira N, Nosaka Y, Shimizu S, Kojima Y, Mizuta K, Kasahara T, Imoto Y, Meehan K, Stocsits R, Wutz G,　Hiraoka Y, Murakawa Y, Yamamoto T, Tachibana K, Peters JM, Mirny LA, Garcia BA, Majewski J, Saitou M. Nucleome programming is required for the foundation of totipotency in mammalian germline development. (2022) EMBO　J., 41(13): e110600. DOI: 10.15252/embj.2022110600

Contact M.Saitou

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