Last Update：2013.02.01
SAITOU Totipotent Epigenome > Project
Project
Summary of the Research
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. An 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. The states of the epigenome play a critical function in determining the growth, differentiation, responses to external stimuli, aging, and diseased conditions of the cells in our body.
On the other hand, the diverse cell types in the body can be broadly classed as either somatic or germ 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.
We have been investigating the mechanism for germ cell specification in mice. Based on the information obtained, in 2011, we succeeded in inducing embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) into epiblast-like cells (EpiLCs), which were in turn induced into PGC-like cells (PGCLCs). Upon transplantation into testes of neonatal mice lacking germ cells, PGCLCs contributed robustly to spermatogenesis, and the resultant sperm contributed to fertile offspring (Hayashi et al., Cell, 2011). This work has been considered as a major breakthrough, which allows the generation of PGCLCs in a relatively large number (~106) and provides a foundation for the reconstitution of whole germ cell development in vitro.
Based on this achievement and to extend the research into a non-human primate, this project explores the following five research objectives:
Research Group for Mouse Germ Cell Development
The work of this group aims for further understanding of the mechanism of mouse germ cell development. Based on the information obtained, the group aims to reconstitute and regulate germ cell development in culture.The projects include 1) the exploration of the mechanism and regulation of PGC proliferation, 2) the induction of spermatogonial stem cells and oocytes from ESCs/iPSCs.
Research Group for Early Development of Cynomolgus Macaque Monkey
The work of this group aims for understanding the mechanism of early development and germ cell specification in Cynomolgus macaque monkey.The projects include 1) the analysis of gene expression regulating early development and PGCs of Cynomolgus macaque monkey, 2) the analysis of X chromosome dynamics in early development of Cynomolgus macaque monkey, 3) the analysis of ESCs of Cynomolgus macaque monkey, 4) the construction of database for genome sequence of Cynomolgus macaque monkey.
Research Group for Reproductive technology of Cynomolgus Macaque Monkey
The work of this group, Shiga University of Medical Science, aims to develop and improve reproductive technologies of Cynomolgus macaque monkey.The projects include 1) the development of micromanipulation and culture of early embryos of Cynomolgus macaque monkey, 2) the establishment of ESCs of Cynomolgus macaque monkey, 3) the development of various reproductive technologies of Cynomolgus macaque monkey.
Research Group for Epigenetic Regulation in Germ Cells
The work of this group aims to understand the mechanism of epigenetic reprogramming in PGCs in the mouse and to create a basis for the analysis of epigenetic reprogramming in Cynomolgus macaque monkey.The projects include 1) the development of a technology to quantify genome-wide epigenetic modifications from a small amount of samples (103~104 cells), 2) the exploration of transcriptional regulation during PGCLC induction, 3) the exploration of genome-wide epigenetic reprogramming during PGCLC induction, 4) the establishment of a basis for epigenome analysis of PGCs of Cynomolgus macaque monkey.
Research Group for human PGC development
The work of this group aims to reconstitute and evaluate human PGC development using iPSCs. This work is performed in collaboration with Drs. Shinya Yamanaka and Kazutoshi Takahashi of Center for iPS Cell Research. The projects include 1) the characterization of iPSCs, 2) the manipulation of gene expression in iPSCs, 3) the induction of human PGCLCs from iPSCs.