基于单细胞组学数据研究早期胚胎发育中表观遗传模式的建立

在早期胚胎发育过程中，表观遗传状态发生了细胞间非对称性的剧烈变化，因此在单细胞层面解析表观遗传模式的建立过程是理解早期胚胎发育机制的重要环节。近期，单细胞表观遗传组学技术得到了长足发展，但是其数据存在覆盖度低、错误率高等特点，这对发展有针对性的分析算法提出了迫切的需求。近几年，申请人发展了一系列表观遗传组学数据分析算法，并揭示了斑马鱼早期胚胎发育的核小体定位模式。在此基础上，本项目针对DNA甲基化和核小体定位这两种重要的表观遗传信息，拟开发有针对性的单细胞组学数据分析算法，并将这些算法应用于小鼠早期胚胎在合子型基因组激活前后的表观遗传组学数据，预期解析早期胚胎发育中表观遗传模式的建立过程。本项目的研究将有助于从单细胞水平深入研究重要生物学过程中的表观遗传调控机制。

During the early embryogenesis, epigenetic statuses change dramatically and are asymmetry between cells. Therefore, to analyze the epigenetic pattern at single cell level is of vital importance to understand the mechanisms of embryogenesis. Recently, significant progresses in single-cell epigenomics techonology have been achieved, but there are still problems such as low coverage and high error rates, which proposed urgent needs for developing specificanalysis algorithms. In recent years, we have developed a series of epigenomics analysis algorithms, and revealed the nucleosome positioning pattern in zebrafish embryo. On this basis, we focus on two important epigenetic types, DNA methylation and nucleosome positioning, and propose to develop efficient algorithms specifically designed for single-cell epigenomics data, then applies these algorithms on single-cell epigenomics data generated in mouse embryos before and after zygotic genome activation, and finally investigate the establishment of epigenetic pattern during early embryogenesis. Our research will contribute to the study of epigenetic regulation in important biological processes at single-cell level.