Using embryo models to understand the development and progression of embryonic lineages: a focus on primordial germ cell development.

Abstract

Recapitulating mammalian cell type differentiation in vitro promises to improve our understanding of how these processes happen in vivo, while bringing additional prospects for biomedical applications. The establishment of stem cell-derived embryo models and embryonic organoids, which have experienced explosive growth over the last few years, open new avenues for research due to their scale, reproducibility, and accessibility. Embryo models mimic various developmental stages, exhibit different degrees of complexity, and can be established across species. Since embryo models exhibit multiple lineages organised spatially and temporally, they are likely to provide cellular niches that, to some degree, recapitulate the embryonic setting and enable "co-development" between cell types and neighbouring populations. One example where this is already apparent is in the case of primordial germ cell-like cells (PGCLCs). While directed differentiation protocols enable the efficient generation of high PGCLC numbers, embryo models provide an attractive alternative as they enable the study of interactions of PGCLCs with neighbouring cells, alongside the regulatory molecular and biophysical mechanisms of PGC competency. Additionally, some embryo models can recapitulate post-specification stages of PGC development (including migration or gametogenesis), mimicking the inductive signals pushing PGCLCs to mature and differentiate, and enabling the study of PGCLC development across stages. Therefore, in vitro models may allow us to address questions of cell type differentiation, and PGC development specifically, that have hitherto been out of reach with existing systems. This review evaluates the current advances in stem cell-based embryo models, with a focus on their potential to model cell type-specific differentiation in general, and in particular to address open questions in PGC development and gametogenesis.