Left yellow panel depicts event that occur naturally. Right purple panel represents human efforts to make synthetic gametes. Fertilization of gametes results in a blastocyst with inner cell mass (ICM) which comprises of pluripotent cells (grown in vitro as ES cells) and further develops into a epiblast-stage embryo where specification into somatic cells and primordial germ cells (PGCs) occurs. PGCs are pluripotent, express nuclear OCT-4, differentiate into gonocytes in testes and primordial follicles in ovaries (please refer to the main text for greater details) and persist in adult gonads as pluripotent, nuclear OCT-4 positive VSELs. Thus in addition to SSCs and OSCs in testes and ovaries , VSELs also exist  as reviewed recently. VSELs self-renew and give rise to progenitors (SSCs in testis and OSCs in ovary) which undergo clonal expansion, meiosis and further differentiation into gametes. Solid blue arrows represent asymmetric cell division of VSELs . Differentiation of ES and iPS cells into synthetic gametes is a distant dream as they do not efficiently differentiate into PGCs. VSELs and OSCs spontaneously differentiate into oocyte-like structures in vitro[43, 63, 74–76, 78, 79] as they are indeed PGCs that survive into adulthood. Limited success has been achieved using bone marrow [27–29], fetal skin  and mesenchymal cells [31–33] possibly because they have VSELs present as a sub-group. Please note that brown color in the yellow panel represents pluripotent nuclear OCT-4 positive cells.