小鼠早期胚胎表观遗传图谱的建立

项目名称： 小鼠早期胚胎表观遗传图谱的建立

项目编号： No.31501178

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 乔云波

作者单位： 中国科学院上海生命科学研究院

项目金额： 20万元

中文摘要： 脊椎动物早期胚胎发育是一个受到严谨精细调控的生命过程。在小鼠胚胎发育早期的原肠运动时期，胚胎各个特定位置的细胞在迁移和分化中，受到外源信号、内源因子及表观遗传调控的综合作用，由多能性的上胚层干细胞发育为不同发育命运的外胚层、中胚层、内胚层和胚外外胚层。表观遗传调控是参与细胞谱系建立和细胞命运决定的重要调控方式，但是目前表观遗传调控是如何参与小鼠胚胎原肠运动时期特异性基因表达模式的建立鲜有报道。本实验室前期工作通过基于单细胞测序的激光显微切割方法，建立了小鼠原肠运动中期全胚胎的转录组图谱。在此基础上，本项目以小鼠胚胎原肠运动中期（E7.0）的胚胎为研究材料，将其切割为前端（A）、后端(P)和胚外外胚层(EXE)三部分，通过超微量的ChIP-seq技术，分析组蛋白修饰和DNA甲基化在胚胎各部分中的分布，建立小鼠早期胚胎的表观遗传修饰全景图谱，以求揭示表观遗传调控网络在早期胚胎模式建成中的功能。

中文关键词： 早期小鼠胚胎；表观遗传组学；组蛋白修饰；DNA甲基化修饰

英文摘要： Early embryo development of vertebrates is a strictly regulated process. During mouse embryo gastrulation stage, embryonic cells in specific locations are modulated by extrinsic signals, intrinsic factors, and epigenetic regulation during cell movements and differentiation, and these cells are developed into an embryo with anterior-posterior and proximal-distal characteristics. Consequently, the gastrulated embryo is specified into ectoderm, mesoderm, endoderm, and extraembryonic ectoderm, with specific gene expression patterns and cell fates. In our previous study, we have established the whole transcriptome of early mouse embryo through single cell sequencing-based laser microdissection technology. Epigenetic regulation is involved cell linage establishment and fate decision, whereas it remains unknown how epigenetic regulation participates in the establishment of embryonic patterning during gastrulation. Mid-gastrula mouse embryos (E7.0) were used in this project, and these embryos were dissected into anterior, posterior, and extraembryonic ectoderm part. Subsequently, the three parts were subjected to microChIP-seq analysis separately to determine the histone modification and DNA methylome, establishing the whole epigenome in early mouse embryo. Finally, we will explore the functions of epigenetic regulation in embryonic patterning in mouse embryo gastrulation stage.

英文关键词： early mouse embryo;epigenome; histone modification;DNA methylation modification