The Human Testis Cell Atlas via Single-cell RNA-seq (Healthy men scRNA-seq data set)
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Human adult spermatogenesis involves a balance of spermatogonial stem cell self renewal and differentiation, alongside complex germline-niche interactions. To better understand, we performed single cell RNA sequencing of ~7000 testis cells from three healthy men of peak reproductive age. Our analyses revealed multiple distinctive transcriptional âstatesâ of self-renewing and differentiating spermatogonia, the cellular stages of gametogenesis, five niche cells (Leydig, Myoid, Sertoli, Endothelial, macrophage) and insights into germline-niche communication. Spermatogenesis was reconstructed computationally, which identified sequential coding, noncoding, and repeat-element transcriptional signatures. A new, developmentally early and likely quiescent spermatogonial state is identified (GFRA1-/ETV5-/ID4+/UTF1+/FGFR3+). Notably, certain epigenetic features combined with nascent transcription analyses suggest considerable plasticity within certain spermatogonial populations/states. Key findings were validated via RNA and protein staining. Taken together, we provided the first âCell Atlasâ of the adult human testis, and provide multiple new insights into germ cell development and germ cell â niche interaction.
人类成年精子发生（spermatogenesis）依赖精原干细胞自我更新与分化的动态平衡，同时伴随复杂的生殖细胞-微环境（germline-niche）相互作用。为深入解析这一生物学过程，我们对3名生育功能巅峰期健康男性的约7000个睾丸细胞开展了单细胞RNA测序（single cell RNA sequencing）。本研究的转录组分析揭示了多个具有独特转录特征的自我更新型与分化型精原细胞状态——后者属于配子发生（gametogenesis）的细胞阶段；同时鉴定出5类核心睾丸微环境细胞：莱迪希细胞（Leydig）、肌样细胞（Myoid）、支持细胞（Sertoli）、内皮细胞（Endothelial）与巨噬细胞（macrophage），并为生殖细胞与微环境的信号交流提供了全新认知。我们通过计算手段重构了精子发生的完整过程，识别出一系列连续的编码基因、非编码基因与重复元件转录特征。本研究还鉴定出一种发育阶段更早、大概率处于静息状态的精原细胞亚型（GFRA1-/ETV5-/ID4+/UTF1+/FGFR3+）。值得注意的是，结合表观遗传特征与新生转录本分析的结果提示，部分精原细胞群体/状态具有显著的细胞可塑性。关键研究发现通过RNA检测与蛋白染色实验得到了验证。综上，本研究构建了首个成人睾丸细胞图谱（Cell Atlas），并为生殖细胞发育以及生殖细胞-微环境互作提供了多项全新见解。
