The mammalian germline is characterized by extensive epigenetic reprogramming during its development into functional eggs and sperm. Specifically, the epigenome requires resetting before parental marks can be established and transmitted to the next generation. In the female germline, X-chromosome inactivation and reactivation are among the most prominent epigenetic reprogramming events, yet very little is known about their kinetics and biological function. Here, we investigate X-inactivation and reactivation dynamics using a tailor-made in vitro system of primordial germ cell-like cell (PGCLC) differentiation from mouse embryonic stem cells. We find that X-inactivation in PGCLCs in vitro and in germ cell-competent epiblast cells in vivo is moderate compared to somatic cells, and frequently characterized by escaping genes. X-inactivation is followed by step-wise X-reactivation, which is mostly completed during meiotic prophase I. Furthermore, we find that PGCLCs which fail to undergo X-inactivation or reactivate too rapidly display impaired meiotic potential. Thus, our data reveal fine-tuned X-chromosome remodelling as a critical feature of female germ cell development towards meiosis and oogenesis.

中文翻译：

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受控的 X 染色体动力学定义了雌性小鼠体外生殖细胞的减数分裂潜力

哺乳动物生殖系的特点是在发育成有功能的卵子和精子期间进行广泛的表观遗传重编程。具体来说，表观基因组需要重置，然后才能建立父母标记并将其传递给下一代。在雌性生殖系中，X 染色体失活和再激活是最突出的表观遗传重编程事件之一，但对其动力学和生物学功能知之甚少。在这里，我们使用量身定制的从小鼠胚胎干细胞分化的原始生殖细胞样细胞 (PGCLC)体外系统研究 X 失活和再激活动力学。我们发现体外PGCLCs和体内生殖细胞感受态外胚层细胞中的X-失活与体细胞相比是温和的，并且经常以逃逸基因为特征。X 失活之后是逐步的 X 再激活，这主要在减数分裂前期 I 完成。此外，我们发现未能经历 X 失活或再激活太快的 PGCLC 显示减数分裂潜力受损。因此，我们的数据揭示了微调的 X 染色体重塑是女性生殖细胞向减数分裂和卵子发生发育的关键特征。