Single-cell multi-omics sequencing of mouse early embryos and embryonic   stem cells

doi:10.1038/cr.2017.82

CORC > 北京大学 > 生命科学学院

	Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells
	Guo, Fan ; Li, Lin ; Li, Jingyun ; Wu, Xinglong ; Hu, Boqiang ; Zhu, Ping ; Wen, Lu ; Tang, Fuchou
刊名	CELL RESEARCH
	2017
关键词	epigenome single-cell COOL-seq multi-omics sequencing mouse preimplantation embryos reprogramming DNA METHYLATION DYNAMICS GENOME-WIDE DETECTION PREIMPLANTATION EMBRYOS EPIGENETIC HETEROGENEITY CHROMATIN ACCESSIBILITY METHYLOME LANDSCAPES PATERNAL GENOME GENE-EXPRESSION REVEALS DEMETHYLATION
DOI	10.1038/cr.2017.82
英文摘要	Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos. We found that within <12 h of fertilization, each individual cell undergoes global genome demethylation together with the rapid and global reprogramming of both maternal and paternal genomes to a highly opened chromatin state. This was followed by decreased openness after the late zygote stage. Furthermore, from the late zygote to the 4-cell stage, the residual DNA methylation is preferentially preserved on intergenic regions of the paternal alleles and intragenic regions of maternal alleles in each individual blastomere. However, chromatin accessibility is similar between paternal and maternal alleles in each individual cell from the late zygote to the blastocyst stage. The binding motifs of several pluripotency regulators are enriched at distal nucleosome depleted regions from as early as the 2-cell stage. This indicates that the cis-regulatory elements of such target genes have been primed to an open state from the 2-cell stage onward, long before pluripotency is eventually established in the ICM of the blastocyst. Genes may be classified into homogeneously open, homogeneously closed and divergent states based on the chromatin accessibility of their promoter regions among individual cells. This can be traced to step-wise transitions during preimplantation development. Our study offers the first single-cell and parental allele-specific analysis of the genome-scale chromatin state and DNA methylation dynamics at single-base resolution in early mouse embryos and provides new insights into the heterogeneous yet highly ordered features of epigenomic reprogramming during this process.; National Natural Science foundation of China [81561138005, 31625018, 81521002]; Beijing Municipal Science and Technology Commission [Z131100005213006]; Peking-Tsinghua Center for Life Sciences; Beijing Advanced Innovation Center for Genomics at Peking University; SCI(E); ARTICLE; 8; 967-988; 27
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/471819]
专题	生命科学学院
推荐引用方式 GB/T 7714	Guo, Fan,Li, Lin,Li, Jingyun,et al. Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells[J]. CELL RESEARCH,2017.
APA	Guo, Fan.,Li, Lin.,Li, Jingyun.,Wu, Xinglong.,Hu, Boqiang.,...&Tang, Fuchou.(2017).Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells.CELL RESEARCH.
MLA	Guo, Fan,et al."Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells".CELL RESEARCH (2017).