Spermatogonial stem cells and their differentiation roadmap throughout marmoset development

Summary Sperm transfer genetic information from one generation to the next. These cells originate from gonocytes, which are specified during early embryonal development. To date however, there is limited information on the transcriptional gatekeepers governing the key events leading to sperm production: transition of gonocytes out of pluripotency around the time of birth, formation of the spermatogonial compartment prior to puberty, and initiation of germ cell differentiation at the time of puberty. We address this knowledge gap by employing the marmoset monkey ( Callithrix jacchus ) as a model for human postnatal testicular development. We analysed the transcriptional profiles of ∼48,000 neonatal, pre-pubertal, pubertal, and adult testicular cells and correlated these with histomorphometric measurements. We uncovered a transcriptional state linking gonocytes and spermatogonia characterized by CITED2 expression. Moreover, we propose NANOS2 and DPPA4 as regulators of spermatogonial plasticity from pre-puberty onwards and identify molecular gatekeepers of male germ cell differentiation.