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

TLDR

Spermatogenesis is a complex, dynamic process essential for male reproduction, driven by spermatogonial stem cells, yet the continuous gene‑expression landscape across all stages remained poorly defined. The study profiled over 62,000 single spermatogenic cells from postnatal day‑6 and adult mice, as well as adult men, generating comprehensive transcriptomes. These data resolved SSCs and progenitor spermatogonia, mapped gene‑expression changes through meiosis and spermiogenesis, and produced distinct signatures for multiple mouse and human spermatogenic cell types, offering a valuable resource for research into SSC biology, male infertility, testicular cancer, contraceptive development, and in‑vitro spermatogenesis.

Abstract

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.