Spermatogonial stem cells (SSCs) are stem cells of the male germ line and support spermatogenesis for a lifetime after puberty by continuously self-renewing and generating committed progenitors. Accordingly, SSCs are defined functionally by their ability to regenerate and maintain spermatogenesis and are detected unequivocally based on their regenerative capacity. Here, we summarize past achievements of morphological and functional studies of SSCs and discuss issues to be addressed in future investigations. Using the mouse as a model organism, our particular foci are the heterogeneity of primitive spermatogonia and the maintenance of and exit from the stem cell state. By comparing to the biology of other stem cell types and organisms, we also propose possibilities and hypotheses for potential mechanisms of SSC fate decision control, involving stochastic entry into the commitment process and the interplay between SSCs and their descendants that coordinates SSC self-renewal and differentiation.
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