scRNA-seq from a single cell M&T-seq: heterogeneity in methylation reprogramming and genome activation in human pre-implantation embryos

The terminally differentiated gametes unite at fertilization to form a totipotent zygote that can differentiate into all cells and tissues of the developing embryo. In mammals, the zygote undergoes several cleavage divisions to form a blastocyst. During this pre-implantation stage, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here we have utilized single cell methylome & transcriptome sequencing (scM&T-seq), a multi-omic method that allows for simultaneous quantification of both mRNA expression and DNA methylation, in human oocytes and a developmental series of human embryos. We fully characterize zygotic and embryonic genome activation (ZGA & EGA, respectively), maternal transcript degradation and map key epigenetic reprogramming events in developmentally viable embryos.