SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate

Abstract

SummarySpecification of primordial germ cells (PGCs) marks the beginning of the totipotent state. However, without a tractable experimental model, the mechanism of human PGC (hPGC) specification remains unclear. Here, we demonstrate specification of hPGC-like cells (hPGCLCs) from germline competent pluripotent stem cells. The characteristics of hPGCLCs are consistent with the embryonic hPGCs and a germline seminoma that share a CD38 cell-surface marker, which collectively defines likely progression of the early human germline. Remarkably, SOX17 is the key regulator of hPGC-like fate, whereas BLIMP1 represses endodermal and other somatic genes during specification of hPGCLCs. Notable mechanistic differences between mouse and human PGC specification could be attributed to their divergent embryonic development and pluripotent states, which might affect other early cell-fate decisions. We have established a foundation for future studies on resetting of the epigenome in hPGCLCs and hPGCs for totipotency and the transmission of genetic and epigenetic information.

The crucial role of Activin A on the formation of primordial germ cell-like cells from skin-derived stem cells in vitro

“…22 More recently, cells derived from human skin were shown to be induced into PGCLCs through iPSCs stages. 20 This shows that SDSCs have the capability of differentiation into PGCs in an in vitro induction system. In the current investigation, we found that cells derived from newborn mouse skin have the potential to transdifferentiate into PGCLCs which express key PGC markers, and present similar dynamic changes in epigenetic modulation to that of developing PGCs in vivo.…”

“…Embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells, such as skinderived stem cells (SDSCs) and pancreatic stem cells, were used for germ cell induction in vitro from mice, [8][9][10][11][12][13][14][15][16] pig, 17 and humans. [18][19][20] SDSCs were shown to be capable of differentiating into different cell types including adipocytes and insulin producing cells in vitro. 21 Particularly, it has Keywords: activin A, differentiation, primordial germ cells, skin-derived stem cells, smad3 been reported that SDSCs isolated from fetal porcine or newborn mouse skin can be differentiated into germ cells or granulosa cells.…”

Functional Human Oocytes Generated by Transfer of Polar Body Genomes

“…However, the complexity of establishing an in vitro system for producing functional haploid human oocytes currently limits this application (Irie et al, 2015;Sasaki et al, 2015). Here, we investigate an alternative approach, namely de novo reconstruction of haploid human oocytes by recycling of PB1 genomes via nuclear transfer into donor cytoplasm (Gurdon, 2015).…”

Germline development in amniotes: A paradigm shift in primordial germ cell specification

“…As novel implantation models 44 and ‘gastrulation’ models using pluripotent stem cells are being developed 45, 46, these may prove to be useful assays to understand the molecular mechanisms that lead to PGC formation in humans. Moreover, directed PGC‐differentiation protocols applied to mouse and human pluripotent stem cells are starting to reveal species‐specific signals regulating specification of PGC‐like cells 47, 48, 49, even though in vivo data might be lacking.…”