On the origin of the human germline

In mice, primordial germ cells (PGCs), the precursors of eggs and sperm, originate from pregastrulation postimplantation embryos. By contrast, the origin of human PGCs (hPGCs) has been less clear and has been difficult to study because of the technical and ethical constraints that limit direct studies on human embryos. In recent years, however, in vitro simulation models using human pluripotent stem cells, together with surrogate non-rodent mammalian embryos, have provided insights and experimental approaches to address this issue. Here, we review these studies, which suggest that the posterior epiblast and/or the nascent amnion in pregastrulation human embryos is a likely source of hPGCs, and that a different gene regulatory network controls PGCs in humans compared with in the mouse. Such studies on the origins and mechanisms of hPGC specification prompt further consideration of the somatic cell fate decisions that occur during early human development.