Mouse primordial germ cells (PGCs) are specified during gastrulation and move anteriorly through the endoderm to the site of the developing gonads, where they continue to mature into either spermatozoa or oocytes. PGC-like cells (PGCLCs) can be derived from embryoid bodies, but these protocols do not recapitulate interactions between developing PGCs and their neighbouring cells and the generation of mature PGCLCs remains a challenge. Here, Naomi Moris and colleagues explore a presumptive PGCLC population in mouse gastruloids, which was recently detected by single-cell sequencing. They use a combination of markers to confirm this population's PGC-like identity and observe that these PGCLCs undergo anterior migration reminiscent of PGC movement in the embryo. This migration is likely endoderm dependent, because gastruloids lacking an endodermal cell population exhibit disrupted PGCLC distributions. Meanwhile, perturbations of the Wnt or FGF signalling pathways result in altered numbers of PGCLCs. Later in gastruloid progression, PGCLCs cluster at the anterior and exhibit epigenetic markers of mature PGCs. Single-cell RNA sequencing suggests that these PGCLCs are comparable to PGCs from E14.5-15.5 embryos, a degree of maturation that is not achieved using traditional in vitro PGCLC methods. Together, this work suggests roles for somatic tissues in PGC development and provides a novel system to model these interactions during PGC maturation.
