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 - Basic Medicine (Core Departments) - Anatomical Science
Anatomy and Cell Biology
The human body consists of 6 trillion cells with at least 210 distinct types. Each of these cells has its own unique character, and it is essential for human life for these cells to develop, maintain themselves, and function appropriately. The essential information code that defines a cell’s unique character is the epigenome, which refers to the whole-genome assembly of epigenetic modifications of chromatin, including DNA methylation and a variety of histone modifications. It is the states of the epigenome that determine the growth, differentiation, responses to external stimuli, aging, and diseased conditions of the cells in our body. By using all the available methodologies in life science as well as by developing new ones, we are aiming to understand the basis of epigenetic regulations and to appropriately control the growth, differentiation, and function of the cells in vitro.

  Mitinori Saitou, M.D., Ph.D.
Professor
Research and Education
All of the diverse cell types in the body can be broadly classed as either somatic or germline cells. In contrast to somatic cells, which work to maintain the constant, stable form and function of an individual organism’s body, germ cells provide the faithfully replicated information needed to establish subsequent generations of individuals. In order to fulfill this role, these cells need to exhibit certain unique properties, including the ability to undergo epigenetic reprogramming, to divide meiotically, and to revert (generally through fusion with another germline cell) to a state of developmental totipotency and maintain that totipotent state until the start of ontogeny. Research in our laboratory is geared to elucidating the developmental bases of germline function at the molecular levels from the very earliest stages of germline development. Specifically, our subjects of interest are the molecular mechanisms, at the levels of both signaling and transcription, involved in the formation of mouse primordial germ cells (PGCs), the cellular progenitors of sperm and oocytes, the genome-wide epigenetic reprogramming that takes place immediately following PGC establishment, the development and application of technologies to enable the analysis of transcriptional regulatory networks at the single-cell level, and ultimately, reconstitution of germ cell development in vitro.
Our studies have so far shown that germ cell specification in mice integrates three key events: repression of the somatic program, reacquisition of potential pluripotency, and genome-wide epigenetic reprogramming. We have identified a PR-domain-containing protein, Blimp1 (also known as Prdm1), as a critical factor for PGC specification. Using a highly representative single-cell microarray technology that we developed, we identified complex but highly ordered genome-wide transcription dynamics associated with PGC specification. This analysis not only demonstrated a dominant role of Blimp1 for the repression of the genes normally down-regulated in PGCs relative to their somatic neighbors, but also revealed the presence of gene expression programs initiated independently from Blimp1. Among such programs, we identified Prdm14, another PR-domain-containing protein, as a key regulator for the reacquisition of potential pluripotency and genome-wide epigenetic reprogramming. The launch of the germ cell lineage in mice, therefore, is orchestrated by two independently acquired PR domain-containing transcriptional regulators, Blimp1 and Prdm14. Furthermore, we have identified a signaling principle in germ cell fate specification. Such studies may provide fundamental information on the reconstruction of the germ cell lineage from pluripotent stem cells in vitro.


Anatomy and Cell Biology
Professor ： Mitinori Saitou
Senior
　Lecturer
：
Katsuhiko Hayashi
Assistant
　Professor
：
Kazuki Kurimoto, Hiroshi Ohta
TEL ： +81-75-753-4335
FAX ： +81-75-751-7286
e-mail ： saitouanat2.med.kyoto-u.ac.jp
Expression of Blimp1 and Prdm14 in mouse embryos at embryonic day 7.0.
Sperm differentiated from induced primordial germ cells from the epiblasts engineered to express GFP (left) are fertilization-competent and can be used to generate normal offspring (right; green shows GFP fluorescence)
Recent Publications
1. Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S., and Saitou, M. (2011). Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell, 146, 519-532.
2. Hirota, T., Ohta, H., Shigeta, M., Niwa, H., and Saitou, M. (2011). Drug-inducible gene recombination by the Dppa3-MER Cre MER transgene in the developmental cycle of the germ cell lineage in mice, Biology of Reproduction, 85, 367-377.
3. Yabuta, Y., Ohta, H., Abe, T., Kurimoro, K., Chuma, S., and Saitou, M. (2011). TDRD5 is required for retrotransposon silencing, chromatoid body assembly and spermiogenesis in mice. The Journal of Cell Biology, 192, 781-795.
4. Yamaji, M., Tanaka, T., Shigeta, M., Chuma, S., Saga, Y., and Saitou, M. (2010). Functional reconstruction of Nanos3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of Nanos3. Reproduction, 139, 381-393.
5. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., and Saitou, M. (2009). A signaling principle for the specification of the germ cell lineage in mice. Cell, 137, 571-584.