Functional primordial germ cell–like cells from pluripotent stem cells in rats
Mami Oikawa, Hisato Kobayashi, Makoto Sanbo, Naoaki Mizuno, Kenyu Iwatsuki, Tomoya Takashima, Keiko Yamauchi, Fumika Yoshida, Takuya Yamamoto, Takashi Shinohara, Hiromitsu Nakauchi, Kazuki Kurimoto, Masumi Hirabayashi, Toshihiro Kobayashi
Abstract
The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on 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 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. When rat PGCLCs are transplanted into the seminiferous tubules of germline-less rats, functional spermatids-that is, those capable of siring viable offspring-are generated. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis.