Single-cell analysis reveals human spermatogenesis and germ cell-sertoli cell interaction

Non-obstructive azoospermia (NOA) is a highly heterogeneous and complex disease. However, there is lack of the research on latent biological mechanisms. Here, we performed single-cell RNA sequencing (scRNA-seq) and Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) on patients with obstructive azoospermia and NOA. Our study identified 12 germ cell subtypes and 8 sertoli cell subtypes. Further analysis identified several stage-specific marker genes of germ cells, such as ID4, TEX19, SCML1, and DMC1 and identified several stage-specific marker genes of sertoli cells, such as SOX2, BEND2, MLC1, PGAM2, and CFH. Furthermore, Notch1/2/3 signaling and integrin were involved in the interaction between germ cells and sertoli cells. Overall, we mapped the scRNA-seq and scATAC-seq of human spermatogenesis, and analyzed germ cell and somatic cell types and their key molecular markers. It gives us a comprehensive insight in spermatogenesis and provide a fresh perspective on diagnosis and treatment for NOA. There were five samples from testicular tissues of two OA patients and three NOA patients.