The Fetal and Infant Human Testis Cell Atlas via Single-cell RNA-seq

Human testis development in prenatal life involves complex changes in germline and somatic cell identity. To better understand, we profiled and analyzed ~32,500 single-cell transcriptomes of testicular cells from embryonic, fetal and infant stages. Our data shows that at 6-7 weeks post-fertilization as the testicular cords are established, the Sertoli and interstitial cells originate from a common heterogeneous progenitor pool, which then resolves into fetal Sertoli cells (expressing tube-forming genes) or interstitial cells (including Leydig-lineage cells expressing steroidogenesis genes). Almost ten weeks later, beginning at 15-16 weeks post-fertilization, the male primordial germ cells exit mitosis, downregulate pluripotent transcription factors and transition into cells that strongly resemble the ‘State 0’ spermatogonia originally defined in the infant and adult testes. Therefore, we termed these fetal spermatogonia ‘State f0’. Taken together, we reveal multiple insights into the coordinated and temporal development of the embryonic, fetal and postnatal male germline together with the somatic niche. We isolated single testicular cell from an infant (5 months old). Two technical replicates were performed.