The dynamic transcriptional profile of sertoli cells during the progression of spermatogenesis

Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2alpha), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1alpha), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility. Genome-wide expression profiling analysis using Illumina next-generation sequencing technology支持细胞（Sertoli cells，SCs）是生精小管内唯一的体细胞，与发育中的生殖细胞紧密结合。其不仅可为生殖细胞提供物理支撑与营养支持，还可分泌对生殖细胞增殖与分化的复杂发育过程至关重要的细胞因子。因此，支持细胞的转录组在精子发生的不同阶段必须快速进行适应性调控。本研究利用RNA测序（RNA sequencing）技术，对小鼠首次精子发生波中5个不同阶段分离得到的纯支持细胞群体进行了全基因组范围的表达谱分析。本研究共重构得到约13901个高可信度、非冗余的编码与非编码转录本，这些转录本具有复杂的可变剪接模式，其中超过45%为已知基因的新型剪接异构体。值得注意的是，其中约五分之一（2939个）基因呈现出动态表达谱，反映了支持细胞在精子发生进程中功能的动态变化；这些基因呈现阶段特异性表达，参与细胞周期调控、代谢与能量产生、视黄酸合成以及血-睾屏障生物发生等生物学过程。最终，调控网络分析鉴定出内皮PAS结构域包含蛋白1（endothelial PAS domain-containing protein 1，EPAS1/Hif2α）、芳烃受体核转位蛋白（aryl hydrocarbon receptor nuclear translocator，ARNT/Hif1α）以及信号转导与转录激活因子1（signal transducer and activator of transcription 1，STAT1）作为驱动支持细胞转录程序的潜在核心调控因子。本研究结果揭示了精子发生进程中支持细胞具有高度可塑性的转录调控全景，并为深入解析支持细胞功能、精子发生过程及其相关疾病（如男性不育）提供了宝贵的研究资源。采用Illumina新一代测序技术开展全基因组表达谱分析