Mechanism and Reconstitution In Vitro of Germ Cell Development in Mammals

The germ cell lineage creates new individuals, perpetuating/diversifying the genetic and epigenetic information across generations. Based on the knowledge obtained through investigations into the mechanisms of germ cell specification and development in mice, we have succeeded in precisely reconstituting the specification and subsequent development of germ cells in culture in both males and females: Embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) are induced into epiblast-like cells (EpiLCs) and then into primordial germ cell-like cells (PGCLCs), which robustly contribute to spermatogenesis and oogenesis and to fertile offspring. This in vitro mouse PGC specification/development system has led to the elucidation of signaling, transcriptional, and epigenetic regulation during germ cell development in a detailed fashion. More recently, based on this system, we and others have demonstrated the induction of human PGCLCs from human ESCs/iPSCs, creating an opportunity for understanding the mechanism of human germ cell development in vitro.