Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the preimplantation embryo’s outer trophectoderm (TE) layer, involved in implantation, while maintaining the inner cell mass (ICM) stem cell population. Using multiple systems biology approaches to compare developmental stages in the early human embryo with single cell transcript data from blastomeres, we have shown that blastomeres considered to be totipotent are not transcriptionally equivalent. Furthermore we have linked the developmental interactome to individual blastomeres and to later cell lineage. This new understanding has clinical implications for understanding the impact of fertility treatments and developmental programming of long term health. Overall design: Human embryos were selected at successive stages of pre-implantation development for RNA extraction and hybridization on Affymetrix microarrays. To that end, we hand-selected embryos according to morphological criteria at four time-points: before fertilisation (embryo), at the begining (4-cell stage) and end (8-cell stage) of embryonic zygotic activation (ETA), and unpon the formation of the Inner cell mass and trophectoderm (blastocyst)