Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment

Human testis development in prenatal life involves complex changes in germline and somatic cell identity. To better understand, we profiled and analyzed similar to 32,500 single-cell transcriptomes of testicular cells from embryonic, fetal, and infant stages. Our data show that at 6-7 weeks postfertilization, 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 10 weeks later, beginning at 14-16 weeks postfertilization, 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 called these fetal spermatogonia state f0.'' Overall, we reveal multiple insights into the coordinated and temporal development of the embryonic, fetal, and postnatal male germline together with the somatic niche.

Automated summary

This study provides insights into the complex changes in cell identity during human testis development in prenatal life, from the establishment of testicular cords to the transitioning of male primordial germ cells into cells resembling f0 spermatogonia. The analysis of single-cell transcriptomes reveals the coordinated and temporal development of embryonic, fetal, and postnatal male germline and somatic niche.