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- SAITOU Totipotent Epigenome
Research Director: Mitinori SAITOU
(Professor, Graduate School of Medicine, Kyoto University)
Research Term: Oct 2011 - Mar 2017
Special Extension Period: Apr 2017 - Mar 2018
Grant Number: JPMJER1104
The germ cell lineage ensures the creation of new individuals, diversifying the genetic and epigenetic information. We have succeeded in inducing mouse embryonic stem cells (mESCs)/induced pluripotent stem cells (miPSCs) into primordial germ cell-like cells (mPGCLCs), which contribute to spermatogenesis, oogenesis, and fertile offspring. Based on this system, we have clarified signaling/transcriptional mechanisms for PGC specification and epigenetic reprogramming in PGCs, succeeded in propagating PGCs in vitro, in inducing spermatogonial stem cell activity in vitro, in clarifying a mechanism for female germ-cell specification, and in generating offspring from infertile sex-chromosome trisomic mice. We have succeeded in inducing human iPSCs (hiPSCs) into hPGCLCs and in clarifying a unique transcriptional mechanism for hPGC specification. Furthermore, using cynomolgus monkeys, we have defined a developmental coordinate of the spectrum of pluripotency among mice, monkeys, and humans, and found that the germ cell lineage in primates is specified in the nascent amnion. We continue to develop a system for further in vitro reconstitution of human germ cell development.