Functional primordial germ cell-like cells from pluripotent stem cells in rats

In vitro generation of germ cells from pluripotent stem cells (PSCs) can crucially impact future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell-like cells (PGCLCs) to produce fertile gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. Notably, rat PGCLCs transplanted into the seminiferous tubules of germline-less rats produce spermatids, leading to the birth of viable offspring. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis. RNA-seq of rat embryonic stem cells (ESCs), epiblast-like cells (EpiLCs), and primordial germ cell like cells (PGCLCs).