Making gametes from pluripotent stem cells: embryonic stem cells or very small embryonic-like stem cells?

The successful differentiation of mouse embryonic stem (mES) cells into haploid spermatids was recently achieved in vitro and published by a group led by 3 first authors including Quan Zhou, Mei Wang and Yan Yuan from China (1). It took almost 45 years to finally reach this stage since mES cells were first reported by Evans and Kaufman (2). The haploid spermatids generated were used for intra-cytoplasmic sperm injection in mouse oocytes and resulted in viable and fertile pups. This success raises hope to treat infertile patients in future. However, it will take much more time since the scientists at present are stuck on the first step itself that involves converting human ES cells into primordial germ cells-like cells (PGCLCs). Just recently Surani’s group reported that SOX17 plays a crucial role in specifying human ES cells into PGCLCs (3). It is basically difficult to convert ES cells into PGCLCs in vitro since it involves epigenetic reprogramming in addition to altered gene expression. Once a robust protocol is established to obtain PGCLCs from ES cells, they can easily be differentiated further into gametes. Thus it will be a while before gametes are obtained starting with human ES cells as concluded recently (4,5).