A single-cell multiomics roadmap of zebrafish spermatogenesis reveals conserved regulatory principles of male germline formation [scATAC-Seq]

Spermatogenesis is a highly complex biological process through which male sperm cells, or spermatozoa, are produced in the testes. Besides enabling the flow of genetic information, spermatogenesis also creates a potential template for inter- and transgenerational inheritance of gene-regulatory states. While extensively studied in mammals, current knowledge of anamniote spermatogenesis remains limited. Here we provide a comprehensive resource consisting of single-cell gene expression and chromatin accessibility data complemented by base-resolution DNA methylome profiling of sorted germ cell populations, obtained from zebrafish (Danio rerio) testes. We identify major germ and somatic cell types implicated in zebrafish spermatogenesis as well as transcriptional drivers associated with each cell type. Moreover, we describe a localised DNA methylome reconfiguration event associated with the spermatocyte stage, and both local and global changes in chromatin accessibility leading to chromatin compaction in spermatids. Finally, we identify loci that escape global chromatin compaction, and which remain accessible thus forming a potential template for the intergenerational transmission of epigenetic states. In summary, our high-resolution cellular atlas of zebrafish spermatogenesis constitutes a major community resource that will enable further studies of germ cell development, evolution, and that will deepen our understanding of diverse molecular mechanisms implicated in genetic and epigenetic inheritance. Overall design: scRNAseq and scATACseq experiments in zebrafish testes.