Germ Cell Biology, Stem Cell Biology
The germ cell lineage ensures the creation of new individuals, thereby perpetuating and diversifying the genetic and epigenetic information across the generations. We have been investigating signaling, global transcription and epigenetic dynamics associated with germ cell specification and development in mice, and have proposed a concept that specification and development of primordial germ cells (PGCs), precursors for the spermatozoa and the oocytes, involve an integration of three key events: repression of the somatic program, re-acquisition of potential pluripotency, and an ensuing genome-wide epigenetic reprogramming. Recently, using pluripotent stem cells [embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)], we have succeeded in precisely reconstituting the specification and development of PGCs in culture: ESCs/iPSCs are induced into epiblast-like cells (EpiLCs) and then into PGC-like cells (PGCLCs), which contribute to sperm and oocytes with full developmental potential. This work will serve as a foundation for systems analysis of germ cell development, including the elucidation of key transcriptional network for germ cell development, the mechanism of genome-wide epigenetic reprogramming, and the mechanism of meiosis, as well as for the reconstitution of the entire germ-cell development process in vitro, not only in mice but also in other mammals, including humans.
- Yamaji, M., Ueda, J., Hayashi, K., Ohta, H., Yabuta, Y., Kurimoto, K., Nakato, R., Shirahige, K., and Saitou, M. PRDM14 ensures naïve pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells, Cell Stem Cell 12, 368-382, (2013).
- Kagiwada, S., Kurimoto, K., Hirota, T., Yamaji, M., and Saitou, M. Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. The EMBO Journal 32, 340-353, (2013).
- Hayashi, K., Ogushi, S., Kurimoto, K., Shimamoto, S., Ohta, H., and Saitou, M. Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science 338, 971-975, (2012).
- Saitou, M., Kagiwada, S., and Kurimoto, K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development, 139, 15-31, (2012).
- Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S., and Saitou, M. Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell 146, 519-532, (2011).