Spermatogonial stem cells (SSCs),namely male germline stem cells,are a subpopulation of type A spermatogonia capable of both self-renewing to maintain stem cell pool and differentiating into mature sperm in mammalian testis. SSCs are previously regarded as the unipotent stem cells,since they can only give rise to spermatids within the seminiferous tubules. However,this concept has recently been changed because numerous studies have demonstrated that SSCs from mice and human testes can acquire pluripotency to become embryonic stem-like (ES-like) cells that are able to differentiate to numerous kinds of cells of three germ layers. In addition,the in vivo and in vitro studies from peers and us have clearly revealed that SSCs directly transdifferentiate into morphologic,phenotypic,and functional cells of other lineages. Dedifferentiation of SSCs to ES-like cells and direct conversion of SSCs to mature cells of other tissues have significant applications for regenerative edicine. We have recently demonstrated that SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such,SSCs could be utilized to offer male gametes for treating male infertility. Notably,great progress has been achieved in uncovering the molecular mechanisms underlying the fate determinations of SSCs. Here we will address the great plasticity of SSCs,with focuses on their self-renewal (proliferation and survival),differentiation,dedifferentiation,transdifferentiation,and translational medicine. We shall also discuss the genetic and epigenetic regulators of SSCs,including gene regulation,signaling transduction pathways,and microRNAs.