In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates.

中文翻译：

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人类和食蟹猴胎儿卵母细胞发育的离体重建

体外卵子发生是阐明人类女性生殖细胞发育及其异常机制的关键。因此，多能干细胞已通过表观遗传重编程被诱导为原始生殖细胞样细胞和卵原细胞，但进一步的重建仍然是一个挑战。在这里，我们展示了人类和食蟹猴（Macaca fasciculis）胎儿卵母细胞发育的离体重建。通过三个月内胎儿卵巢重新聚集的优化培养，人和猴子的卵原细胞进入并完成第一个减数分裂前期，分化为形成原始卵泡的双线期卵母细胞，这是成人卵子发生的来源。胎儿卵母细胞体外发育的细胞学和转录组进展与体内的进展密切相关。对人类、猴子和小鼠单细胞转录组的比较揭示了驱动胎儿卵母细胞发育的灵长类动物特异性和保守程序，前者包括卵原细胞到卵母细胞转变时的独特转录组转变，后者包括两条活性 X 染色体，几乎没有X染色体上调。我们的研究为实现人类体外卵子发生迈出了关键的一步，并揭示了灵长类动物胎儿卵母细胞发育的显着特征。