The Mammalian Spermatogenesis Single-Cell Transcriptome, from Spermatogonial Stem Cells to Spermatids

• Published in: Cell reports (Cambridge) Vol. 25; no. 6; pp. 1650 - 1667.e8
• Main Authors: Hermann, Brian P., Cheng, Keren, Singh, Anukriti, Roa-De La Cruz, Lorena, Mutoji, Kazadi N., Chen, I-Chung, Gildersleeve, Heidi, Lehle, Jake D., Mayo, Max, Westernströer, Birgit, Law, Nathan C., Oatley, Melissa J., Velte, Ellen K., Niedenberger, Bryan A., Fritze, Danielle, Silber, Sherman, Geyer, Christopher B., Oatley, Jon M., McCarrey, John R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.11.2018; Elsevier
• Subjects: Adult; Aging - genetics; Animals; Cell Differentiation; continuum; Gene Expression Regulation, Developmental; Haploidy; heterogeneity; human; Humans; Male; male germ cells; Mammals - genetics; Meiosis; Mice, Inbred C57BL; mouse; RNA; Signal Transduction; Single-Cell Analysis; Spermatids - cytology; Spermatids - metabolism; Spermatogenesis - genetics; Spermatogonia - cytology; Spermatogonia - metabolism; spermiogenesis; Stem Cells - cytology; Stem Cells - metabolism; Testis - cytology; Transcriptome - genetics; mouse; continuum; meiosis; RNA; spermiogenesis; male germ cells; human; heterogeneity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.10.026

Spermatogenesis is a complex and dynamic cellular differentiation process critical to male reproduction and sustained by spermatogonial stem cells (SSCs). Although patterns of gene expression have been described for aggregates of certain spermatogenic cell types, the full continuum of gene expression patterns underlying ongoing spermatogenesis in steady state was previously unclear. Here, we catalog single-cell transcriptomes for >62,000 individual spermatogenic cells from immature (postnatal day 6) and adult male mice and adult men. This allowed us to resolve SSC and progenitor spermatogonia, elucidate the full range of gene expression changes during male meiosis and spermiogenesis, and derive unique gene expression signatures for multiple mouse and human spermatogenic cell types and/or subtypes. These transcriptome datasets provide an information-rich resource for studies of SSCs, male meiosis, testicular cancer, male infertility, or contraceptive development, as well as a gene expression roadmap to be emulated in efforts to achieve spermatogenesis in vitro. [Display omitted] •Single-cell transcriptomes of >62,000 spermatogenic cells from mice and humans•Human SSC fate regulation pathways match those of functionally defined mouse SSCs•The hepatic stellate cell activation pathway is associated with SSC fate•Unique 3-gene identifiers distinguish 11 spermatogenic cell types in mice and humans Hermann et al. present single-cell transcriptomes from >62,000 individual spermatogenic cells from immature and adult male mice and adult men. Their analysis facilitates resolution of SSCs and progenitor spermatogonia, elucidates the full range of gene expression changes during male meiosis and spermiogenesis, and derives unique gene expression signatures for eleven mouse and human spermatogenic cell types.