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Background Objectives Materials and methods Results and conclusion Spermatogonial stem cells (SSCs) are essential for adult spermatogenesis. Themolecular mechanisms driving SSC generation are poorly understood.Zou et al. reported that the precursor cells that give rise to SSCs–prospermatogonia (ProSG) require the RNA‐binding protein, DDX20, in orderto undergo the obligatory proliferative re‐activation step that proceeds SSC formation.Literature search.We summarize the authors' discovery that the RNA‐binding protein, DDX20, iscritical for driving the proliferative re‐activation of ProSG, a key step that proceeds SSC generation in vivo. They provide evidence that DDX20 performs this role through its ability to promote the translation of mRNAs encoding proteins known to be essential for cell‐cycle and spermatogonial homeostasis. It remains to be determined whether this role is conserved inhumans. It will also be interesting to elucidate whether other post‐transcriptional regulators also have roles in early germ cell development. More broadly, it will be fascinating to determine whether post‐transcriptional regulators workin concert with transcriptional regulators to drive germ‐cell development. [ABSTRACT FROM AUTHOR]

In the developing mammalian testis, only a small proportion of fetal and neonatal prospermatogonia give rise to the foundational pool of spermatogonial stem cells (SSCs). Multiple lines of evidence have suggested the determination of which prospermatogonia give rise to foundational SSCs is not random, but is rather predetermined, such that foundational SSCs are ensured to develop advantageous characteristics such as enhanced genetic integrity. Here I suggest that differential epigenetic programing contributes to the molecular mechanisms by which an early subset of developing prospermatogonia becomes predetermined to form the foundational pool of SSCs. This would include epigenetic programing that promotes active expression of genes needed to develop advantageous characteristics, as well as differential epigenetic priming, which bookmarks genes that comprise the SSC‐specific transcriptome to become activated when foundational SSCs appear in the postnatal testis. I suggest that, together, differential epigenetic programing and epigenetic priming contribute to the molecular mechanisms by which an early subset of developing prospermatogonia becomes predetermined to form the foundational pool of SSCs. [ABSTRACT FROM AUTHOR]

Background: The germline serves as a conduit for transmission of genetic and epigenetic information from one generation to the next. In males, spermatozoa are the final carriers of inheritance and their continual production is supported by a foundational population of spermatogonial stem cells (SSCs) that forms from prospermatogonial precursors during the early stages of neonatal development. In mammals, the timing for which SSCs are specified and the underlying mechanisms guiding this process remain to be completely understood. Objectives: To propose an evolving concept for how the foundational SSC population is established. Materials and methods: This review summarizes recent and historical findings from peer‐reviewed publications made primarily with mouse models while incorporating limited studies from humans and livestock. Results and conclusion: Establishment of the SSC population appears to follow a biphasic pattern involving a period of fate programming followed by an establishment phase that culminates in formation of the SSC population. This model for establishment of the foundational SSC population from precursors is anticipated to extend across mammalian species and include humans and livestock, albeit on different timescales. [ABSTRACT FROM AUTHOR]