Human pluripotent stem cells have the remarkable property of self-renewal and the ability to differentiate into every cell type in the body including germ cells. One of the major uses of human pluripotent stem cells is to increase our fundamental understanding of the molecular events occurring in the peri-implantation window of human life. This is the time when the human embryo implants into the uterus, organizes, and pluripotency of the epiblast gives way to lineage differentiation and cell fate commitment. Using combinations of CRISPR/Cas9, genomics, single cell transcriptomics and human embryo attachment culture, my laboratory has uncovered some of the major cell lineage transitions occurring in the peri-implantation window of human development including the molecular events involved in the transition from naïve to primed human pluripotency, and the molecular events involved in establishing human germ cell fate. Using a new computational pipeline called time constrained URD to simultaneously track cell fates of somatic and germ cells differentiating in three dimensional (3D) disorganized aggregates, my laboratory can now show that the differentiation of human germ cells from pluripotent stem cells involves first a reversion of primed pluripotency to a transitional primed/naïve-like state, which is also found in the human embryo at day 12. This is followed by differentiation to lineage primed progenitors in response to BMP4, that become germ cells extraembryonic mesoderm, trophoblast and gastrulating cells. We also show that the differentiation of germ cells in disorganized aggregates is equivalent to the differentiation in 3D modelled embryonic sacs. Taken together the use of pluripotent stem cells to model human development, particularly in the peri-implantation window where studies in humans are almost impossible, provides an unprecedented opportunity to understand and in the future develop strategies to prevent pregnancy loss.