小鼠早期胚胎表观遗传图谱的建立

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.

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。

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，本项目通过开发基于少量细胞的表观遗传学研究手段，深入研究了小鼠原肠运动过程中胚胎各胚层的表观遗传修饰变化模式，发现并验证了发育相关基因在原肠胚不同区域内表观调控机制的差别，并进一步研究了小鼠胚胎干细胞神经分化过程中TGFbeta信号和表观遗传调控对细胞命运决定的协同调控作用。本项目的研究成果将加深对哺乳动物早期胚胎发育过程中分子调控机制的认识，从而推动再生医学等的发展。