Generation of functional primordial germ cells from pluripotent stem cells

Primordial germ cells (PGCs), origin of the germ cell lineage, arise from epiblast cells in response to BMP4 secreted by adjacent extraembryonic ectoderm. We recently reconstituted the PGC specification in vitro using mouse embryonic stem cells (mESCs) as well as induced pluripotent stem cells (iPSCs). In the culture system, mESCs/iPSCs first differentiated into epiblastlike cells (EpiLCs) and then induced PGC-like cells from the EpiLCs. This manner of differentiation from mESCs to PGCs reproduces the manner of PGC specification in vivo. PGCs produced from mESCs, termed PGC-like cells (PGCLCs), were fully potent, since they differentiated into spermatozoa and in turn the fertilized eggs with the spermatozoa gave rise to healthy individuals. Although many attempts have been made to produce fully potent PGCs, this study was the first study demonstrating the successful production of healthy individuals from PGCLCs. This achievement was made possible by knowledge accumulated on the manner of PGC specification in vivo, the nature of self-renewing pluripotent stem cells, and growth factors endowing EpiLC formation and PGCLC induction in vitro. This article reviews the research advance that made it possible to reconstitute PGC specification in vitro from mESCs.