Single-Cell RNA Sequencing of the Cynomolgus Macaque Testis Reveals Conserved Transcriptional Profiles during Mammalian Spermatogenesis.

Abstract

Spermatogenesis is highly orchestrated and involves the differentiation of diploid spermatogonia into haploid sperm. The process is driven by spermatogonial stem cells (SSCs). SSCs undergo mitotic self-renewal, whereas sub-populations undergo differentiation and later gain competence to initiate meiosis. Here, we describe a high-resolution single-cell RNA-seq atlas of cells derived from Cynomolgus macaque testis. We identify gene signatures that define spermatogonial populations and explore self-renewal versus differentiation dynamics. We detail transcriptional changes occurring over the entire process of spermatogenesis and highlight the concerted activity of DNA damage response (DDR) pathway genes, which have dual roles in maintaining genomic integrity and effecting meiotic sex chromosome inactivation (MSCI). We show remarkable similarities and differences in gene expression during spermatogenesis with two other eutherian mammals, i.e., mouse and humans. Sex chromosome expression in the male germline in all three species demonstrates conserved features of MSCI but divergent multicopy and ampliconic gene content.