Brief history, pitfalls, and prospects of mammalian spermatogonial stem cell research.

Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis. During the last decade, several techniques for the manipulation of this cell type have been developed; as a result, SSCs can now be subjected to long-term in vitro expansion and genetically manipulated for knockout mouse production. These techniques have allowed SSCs to serve as a new target for animal transgenesis, which may provide an alternative to embryonic stem (ES) cells. Furthermore, SSCs may be converted into ES-like cells, demonstrating that the postnatal testis is a source of pluripotent stem cells. These techniques were first established in mice, but they are currently being extended to other animal species. SSC-based technologies will be useful in agriculture and medicine and will also provide valuable opportunities to study SSC biology. The mechanisms of self-renewal division and differentiation and the regulation of pluripotency in SSCs are now being studied at the molecular level. However, some technical and conceptual pitfalls must be kept in mind when designing and analyzing experimental results. Nevertheless, these advances in SSC research will provide valuable insight into the study of mammalian stem cell systems.