Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Cell Rep. 2019 Feb 5;26(6):1501-1517.e4. doi: 10.1016/j.celrep.2019.01.045.
Spermatogenesis has been intensely studied in rodents but remains poorly understood in humans. Here, we used single-cell RNA sequencing to analyze human testes. Clustering analysis of neonatal testes reveals several cell subsets, including cell populations with characteristics of primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). In adult testes, we identify four undifferentiated spermatogonia (SPG) clusters, each of which expresses specific marker genes. We identify protein markers for the most primitive SPG state, allowing us to purify this likely SSC-enriched cell subset. We map the timeline of male germ cell development from PGCs through fetal germ cells to differentiating adult SPG stages. We also define somatic cell subsets in both neonatal and adult testes and trace their developmental trajectories. Our data provide a blueprint of the developing human male germline and supporting somatic cells. The PGC-like and SSC markers are candidates to be used for SSC therapy to treat infertility.
精原细胞发生在啮齿动物中被深入研究，但在人类中仍知之甚少。在这里，我们使用单细胞 RNA 测序来分析人类睾丸。对新生儿睾丸的聚类分析揭示了几个细胞亚群，包括具有原始生殖细胞 (PGC) 和精原干细胞 (SSC) 特征的细胞群体。在成人睾丸中，我们鉴定出四个未分化的精原细胞 (SPG) 簇，每个簇都表达特定的标记基因。我们鉴定出最原始的 SPG 状态的蛋白质标记，从而能够纯化这个可能富含 SSC 的细胞亚群。我们描绘了从 PGC 到胎儿生殖细胞再到分化的成人 SPG 阶段的男性生殖细胞发育的时间表。我们还在新生儿和成人睾丸中定义了体细胞亚群，并追踪它们的发育轨迹。我们的数据为发育中的人类男性生殖系和支持体细胞提供了蓝图。PGC 样和 SSC 标记物是用于 SSC 治疗不孕的候选物。
