On the origin of the human germline

Abstract

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.

Testing the role of SOX15 in human primordial germ cell fate

“…and NANOG as shown by qPCR analysis ( Figure 4A) (Z test with Holm-Bonferroni correction, p < 0.05); PRDM14, VENTX, SOX15, and NANOG are known to be associated with germ cell identity 1,2 , perhaps suggesting a compensatory effect. Notably, the upregulation of SOX15 implies negative feedback, while AKAP1, VENTX, and BEND4 are known targets of PRDM14 in hPGCLCs 6 , so their upregulation may be indirect.…”

Advances in epigenetics link genetics to the environment and disease

“…These studies demonstrated that differentially expressed states can be transmitted across cell divisions, once they are established and in the absence of the original signal. Studies of cellular reprogramming in the germline and early embryogenesis [19][20][21][22] , during induced pluripotency (iPS) 23,24 , or upon somatic nuclear transfer 25,26 have shown that chromatin and DNA methylation act as important 'epigenetic barriers' (Fig. 1) that prevent changes in gene expression and cell identity.…”

Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage

“…Extensive epigenetic reprogramming follows, which includes the erasure of imprints and potentially epimutations for the restoration of totipotency (Hill et al, 2018;Kurimoto et al, 2008;Tang et al, 2016). While the principles of mammalian germline development are emerging, so are some important differences and gaps in our knowledge (Kobayashi and Surani, 2018;Saitou and Miyauchi, 2016).…”