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.多能干细胞（PSCs）体外诱导生成生殖细胞，对未来生殖医学与动物育种具有至关重要的影响。十年前，小鼠体外配子发生体系已成功建立。然而，除小鼠外，尚无其他物种能够通过诱导原始生殖细胞样细胞（PGCLCs）产生可育配子。本研究成功实现了从大鼠多能干细胞诱导获得功能性原始生殖细胞样细胞：我们发现悬浮聚集体中的上胚层样细胞可分化为大鼠PGCLCs；性腺体细胞可支持该PGCLCs的成熟与表观遗传重编程。值得注意的是，将大鼠PGCLCs移植至生殖系缺失大鼠的生精小管后，可产生精子细胞，并最终获得存活的子代个体。本研究基于大鼠模型所获得的研究结论，将阐明体外配子发生技术广泛应用所必需的保守与分化机制。