Sex Specification and Heterogeneity of Primordial Germ Cells in Mice.

Sex Specification and Heterogeneity of Primordial Germ Cells in Mice.
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DOI:
10.1371/journal.pone.0144836
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Kono T
Kono T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sakashita A;Kawabata Y;Jincho Y;Tajima S;Kumamoto S;Kobayashi H;Matsui Y;Kono T

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在小鼠中,原始生殖细胞在胚胎第13.5天(E13.5)迁移到生殖嵴中,然后在那里它们受到性别特异性的命运,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知之甚少。本研究旨在探讨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对E13.5雌性和雄性小鼠原始生殖细胞进行RNA测序(seq)。我们在雌性和雄性原始生殖细胞中分别鉴定了651和428个差异表达的转录本(>2倍,P < 0.05)。其中,许多转录因子被确定。基因本体论和网络分析揭示了不同的功能,所确定的女性和男性特定的基因,与原始生殖细胞收购所需的性别特异性的属性分化成生殖细胞。此外,DNA甲基化和组蛋白修饰的ChIP-seq分析表明,低甲基化的基因启动子区域与H3 K4 me 3和H3 K27 me 3结合。我们的全球转录组数据显示,在小鼠中,原始生殖细胞通过E13.5决定性地分配给性别特异性分化程序,这是重要生殖细胞发育所必需的。
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.