Abstract
Continuous sperm production is not necessary for the survival of the organism, but it is essential to maintain a species. To generate sperm, the diploid spermatogonial stem cells in the testis must undergo a series of mitotic and meiotic divisions, and postmeiotic morphological changes. To illuminate germline intrinsic and extrinsic programs, we performed single-cell RNA sequencing on ~35K cells from the adult mouse testis. This analysis provides a comprehensive molecular atlas of the testis, identifying known and novel cell types. We demonstrate for the first time the continuous nature of germ cell differentiation, and provide molecular signatures for germ cell states. Furthermore, differential gene expression analysis across germ cell populations yields subtype-specific molecular markers and identifies several candidate novel regulators of spermatogenesis. Finally, we demonstrated that the germ and somatic cell subtypes correspond to known histologically defined cell types residing at different stages of seminiferous epithelial cycle. Taken together our results unveil the complexity of the testis and provide a global, unbiased roadmap of the in vivo gametogenesis program.
