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There are trillions of cells, of nearly 300 different varieties, in the human body. Yet all of these cells arise from a single progenitor: the zygote that is generated from combination of sperm and oocyte. And one of earliest things the zygote does during development is to set aside a group of cells, the primordial germ cells, which go on to generate all of the sperm/oocytes of that person. Using pluripotent stem cells, we can recapitulate this early embryological decision and create a reliable and robust source of primordial germ cells that would be a tremendous resource for understanding reproductive biology and treating infertility. Using genetic tailoring technologies (TALEN/CRISPR), we have modified human embryonic stem cell lines to “knock-in” fluorescent reporters at gene loci that are specifically expressed during primordial germ cell development. With these tools, we have isolated primordial germ cell precursors at unique developmental milestones and used global gene expression analysis to identify novel pathways that are involved in germ cell ontogeny. By developing a molecular roadmap of primordial germ cell differentiation, we aim to explore mechanisms of epigenetic regulation during germ cell ontogeny, identify pathways that drive further differentiation into functional gametes and ultimately, to employ patient-specific pluripotent stem cells to provide an alternative source of gametes for individuals and couples affected by infertility.