Recent advances in human germ cell derivation have resulted in the production of male and female gametes from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) in vitro. So far, this process has been relatively inefficient as compared to gametes derived from mouse ES cells. To better understand the developmental pathways that result in the production of germ cells in vivo, we seek to model germline derivation by recapitulating some of the cellular and signaling events in an in vitro platform. Our primary objective is to identify novel genes and molecules that specify a germ cell fate in hESCs and iPSCs. We note that we have already identified several critical genes that help induce a primordial germ cell-like fate and can even induce meiosis in these cells. To improve the overall efficiency and maturity of these germ cells, we will use the novel factors in our in vitro approaches. Ultimately, we aim to use this system to generate germ cells from patients with genetic deletions and who cannot make germ cells. To achieve this, we will ‘repair’ genetic deletions in the Y chromosome by using gene complementation. In this manner, we can further understand the developmental contribution of key genes present on the Y chromosome to germline development.