Methods of generating a synthetic embryo are provided. Accordingly, there is provided a method of generating a synthetic embryo comprising inducing expression of a factor that induces differentiation to trophectoderm cells in a subpopulation of naïve pluripotent stem cells (PSCs) to obtain a trophectoderm primed cells; inducing expression of a factor that induces differentiation to extra embryonic primitive endodermal cells in a second subpopulation of naïve PSCs to obtain extra embryonic primitive endodermal primed cells; and mixing said trophectoderm primed cells and said extra embryonic primitive endodermal primed cells with naïve PSCs under conditions that allow formation of aggregated cells. Also provided are articles of manufactures, mixtures and aggregates of cells and methods of using same.