Single Cell DNA Methylome Sequencing of Human Preimplantation Embryos

Although the DNA methylome of human early embryos has been analyzed, some of the key features have not been addressed to date. Here, we performed single-cell DNA methylome sequencing for human preimplantation embryos and found that tens of thousands of genomic loci exhibited de novo DNA methylation. This finding indicates that genome-wide DNA methylation reprogramming during preimplantation development is a dynamic balance between strong global demethylation and significant focused re-methylation. Furthermore, the demethylation of the paternal genome is much faster and thorough than that of the maternal genome. From the 2-cell to post-implantation stage, methylation of the paternal genome is consistently lower than that on the maternal genome. We also showed that the genetic lineage of the early blastomeres could be traced by DNA methylation analysis. Our work paves the way for deciphering the secrets of DNA methylation reprogramming in human early embryos. Overall design: We did single cell PBAT DNA methylome sequencing analysis for cells from human mature oocytes and preimplantation embryos. For each individual cell, we sequenced 8.4 Gb of data on average.