Germline development in rat revealed by visualization and deletion of Prdm14
Germline development in rat revealed by visualization and deletion of Prdm14
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DOI：
10.1242/dev.183798
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发表时间：
2020-02-01
期刊：
影响因子：
4.6
通讯作者：
Hirabayashi, Masumi
中科院分区：
文献类型：
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作者：
Kobayashi, Toshihiro;Kobayashi, Hisato;Hirabayashi, Masumi
原始生殖细胞（PGCs）是生殖系的创始细胞，在哺乳动物的原肠胚形成前被指定，随后向性腺迁移以成熟为功能配子。在这里，我们研究了PGC的发展在大鼠中，通过遗传修饰Prdm 14，一个独特的标志物和一个必不可少的PGC转录调节因子。我们跟踪大鼠PGC的发展，第一次，从规格，直到性别决定阶段在胎儿性腺中使用Prdm 14 H2 BVenus敲入大鼠。通过分析Prdm 14缺陷的大鼠胚胎，我们发现Prdm 14在PGC特异性中的关键作用在大鼠和小鼠之间是保守的。值得注意的是，Prdm 14的缺失完全废除了PGC程序，如生殖细胞标志物和多能性基因的维持和/或激活失败所证明的。最后，我们分析了大鼠植入后上胚层和所有PGC阶段的转录组，以揭示在每个转换点不同基因集的富集，从而为大鼠PGC发育提供准确的转录时间轴。因此，本研究中获得的新型转基因大鼠和数据集将推进我们对哺乳动物生殖系发育的保守特征与物种特异性特征的认识。
Primordial germ cells (PGCs), the founder cells of the germline, are specified in pre-gastrulating embryos in mammals, and subsequently migrate towards gonads to mature into functional gametes. Here, we investigated PGC development in rats, by genetically modifying Prdm14, a unique marker and an essential PGC transcriptional regulator. We trace PGC development in rats, for the first time, from specification until the sex determination stage in fetal gonads using Prdm14 H2BVenus knock-in rats. We uncover that the crucial role of Prdm14 in PGC specification is conserved between rat and mice, by analyzing Prdm14-deficient rat embryos. Notably, loss of Prdm14 completely abrogates the PGC program, as demonstrated by failure of the maintenance and/or activation of germ cell markers and pluripotency genes. Finally, we profile the transcriptome of the post-implantation epiblast and all PGC stages in rat to reveal enrichment of distinct gene sets at each transition point, thereby providing an accurate transcriptional timeline for rat PGC development. Thus, the novel genetically modified rats and data sets obtained in this study will advance our knowledge on conserved versus species-specific features for germline development in mammals.