唯支持细胞综合征（SCOS）是男性不育症中的严重疾病，表现为生精小管内部精细胞缺失，仅有Sertoli细胞存活。研究表明Sertoli细胞异常与SCOS之间存在较大关联。然而，由于缺乏合适的研究体系，背后的致病机理仍有待进一步阐明。人类Sertoli细胞的体外重编程体系为Sertoli细胞及SCOS的致病机理的研究提供了新途径。本课题拟在建立SCOS分型的基础上，利用微量基因组及10X单细胞转录组测序技术，分析SCOS患者的Sertoli细胞基因组及全转录组特征，筛选与生殖相关的突变及异常表达基因；利用基因打靶技术进一步完善Sertoli细胞的重编程平台；结合细胞免疫荧光、电镜以及转录组测序分析技术，研究上述候选突变及异常表达基因对下游靶基因的作用、对Sertoli细胞发育及亚细胞结构的影响。本研究将有助于阐明与Sertoli细胞有关的SCOS致病机理并有望获得一批新的SCOS标志。

Sertoli cell only syndrome (SCOS) is a serious disease in male infertility, which is manifested by the absence of spermatogenic cells inside the seminiferous tubules, and only Sertoli cells survive. Studies have shown the large correlation between the abnormal Sertoli cells and SCOS. However, due to the lack of research system, the underlying mechanism remains to be further clarified. Sertoli cell reprogramming in vitro provides a new way to study the abnormal features and pathogenic mechanism of Sertoli cells in SCOS patients. In this study we will firstly establish aclassification criteria for SCOS, then use microgenomic and 10X single cell sequencing to analyze the genome and transcriptome of Sertoli cells in SCOS, and screen out candidate mutant genes and abnormally expressed genes related to reproduction; Further improve the Sertoli cell in vitro reprogramming platform by gene targeting technology; Combining with cell immunofluorescence, electron microscopy and whole transcriptome sequencing technology, we will study the effect of the above candidate mutations and abnormal gene expression on the transcription of downstream target genes, the effects of androgen secretion by Sertoli cells, the development of Sertoli cells and the subcellular structure. This study will help elucidate the pathogenesis of SCOS related to Sertoli cell function and development. and verify a batch of new SCOS markers.