Spermatogonial Stem Cells and Spermatogenesis

Hallmarks of spermatogenesis are the maintenance of a stem cell pool of germ cells in adults and spermiogenesis in which round haploid spermatids are transformed into spermatozoa. We have identified a male-specific nuclear protein required for maintenance of stem cells and its genetic ablation restricts spermatogenesis to a single wave after birth. Adults are infertile and mutant mice lacking germ cells provide a model of the Sertoli-cell-only syndrome in humans. We also have discovered a germ cell nuclear protein, BTBD18, that occupies pachytene piRNA-producing loci. Ablation of the gene in mice disrupts piRNA biogenesis, prevents spermiogenesis, and results in male sterility. Transcriptome profiling, chromatin accessibility, and RNA polymerase II occupancy demonstrate that BTBD18 facilitates expression of pachytene piRNA precursors by promoting transcription elongation. Gene editing of downstream targets provides mechanistic insight into the observed phenotype.