Single-cell multi-omics sequencing of human early embryos
DNA methylation, chromatin states, and their interrelationships represent critical epigenetic information, but those are largely unknown in human early embryos. Here, we apply scCOOL-seq (Chromatin Overall Omic-scale Landscape Sequencing) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of paternal genome is already more open than that of maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation and those with high variations in chromatin accessibility tend to be two different sets. Furthermore, 1,797 (35%) out of 5,155 widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development. Overall design: In total, we analyzed 265 single cells (13 sperm, 9 oocytes, 10 zygotes, 14 2-cell blastomeres, 26 4-cell blastomeres, 48 8-cell blastomeres, 25 morulae blastomeres, 50 ICM, 48 TE and 22 hESCs) as well as 23 alpha-Amanitin treated 8-cell blastomeres.
External Link: /pubmed:29915357