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 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.

产前人类睾丸发育涉及种系和体细胞特性的复杂变化。为了更好地理解，我们从胚胎、胎儿和婴儿阶段分析了约 32,500 个睾丸细胞的单细胞转录组。我们的数据显示，在受精后 6-7 周，随着睾丸索的建立，支持细胞和间质细胞起源于一个共同的异质祖细胞池，然后分解为胎儿支持细胞（表达管形成基因）或间质细胞（包括表达类固醇生成基因的 Leydig 系细胞）。大约 10 周后，从受精后 14-16 周开始，雄性原始生殖细胞退出有丝分裂，下调多能转录因子，并转变为与最初在婴儿和成人睾丸中定义的状态 0 精原细胞非常相似的细胞。因此，我们将这些胎儿精原细胞称为“状态 f0”。总体而言，我们揭示了胚胎、胎儿和出生后雄性生殖系与体细胞生态位的协调和时间发育的多种见解。