Sakashita Akihiko, Kawabata Yukiko, Jincho Yuko, Tajima Shiun, Kumamoto Soichiro, Kobayashi Hisato, Matsui Yasuhisa, Kono Tomohiro
Department of Bioscience, Tokyo University of Agriculture, Setagaya, Tokyo, Japan.
NODAI Genome Research Center, Tokyo University of Agriculture, Setagaya, Tokyo, Japan.
PLoS One. 2015 Dec 23;10(12):e0144836. doi: 10.1371/journal.pone.0144836. eCollection 2015.
In mice, primordial germ cells migrate into the genital ridges by embryonic day 13.5 (E13.5), where they are then subjected to a sex-specific fate with female and male primordial germ cells undergoing mitotic arrest and meiosis, respectively. However, the sex-specific basis of primordial germ cell differentiation is poorly understood. The aim of this study was to investigate the sex-specific features of mouse primordial germ cells. We performed RNA-sequencing (seq) of E13.5 female and male mouse primordial germ cells using next-generation sequencing. We identified 651 and 428 differentially expressed transcripts (>2-fold, P < 0.05) in female and male primordial germ cells, respectively. Of these, many transcription factors were identified. Gene ontology and network analysis revealed differing functions of the identified female- and male-specific genes that were associated with primordial germ cell acquisition of sex-specific properties required for differentiation into germ cells. Furthermore, DNA methylation and ChIP-seq analysis of histone modifications showed that hypomethylated gene promoter regions were bound with H3K4me3 and H3K27me3. Our global transcriptome data showed that in mice, primordial germ cells are decisively assigned to a sex-specific differentiation program by E13.5, which is necessary for the development of vital germ cells.
在小鼠中，原始生殖细胞在胚胎第13.5天（E13.5）迁移至生殖嵴，在那里它们随后经历性别特异性命运，雌性和雄性原始生殖细胞分别经历有丝分裂停滞和减数分裂。然而，原始生殖细胞分化的性别特异性基础仍知之甚少。本研究的目的是探究小鼠原始生殖细胞的性别特异性特征。我们使用下一代测序技术对E13.5雌性和雄性小鼠原始生殖细胞进行了RNA测序（RNA-seq）。我们分别在雌性和雄性原始生殖细胞中鉴定出651个和428个差异表达转录本（>2倍，P<0.05）。其中，鉴定出了许多转录因子。基因本体和网络分析揭示了所鉴定的雌性和雄性特异性基因的不同功能，这些基因与原始生殖细胞获得分化为生殖细胞所需的性别特异性特性有关。此外，DNA甲基化和组蛋白修饰的ChIP-seq分析表明，低甲基化基因启动子区域与H3K4me3和H3K27me3结合。我们的全局转录组数据表明，在小鼠中，原始生殖细胞在E13.5时被决定性地分配到性别特异性分化程序中，这对于重要生殖细胞的发育是必要的。
