Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome  

作　　者：Liang-Yu Zhao Peng Li Chen-Cheng Yao Ru-Hui Tian Yu-Xin Tang Yu-Zhuo Chen Zhi Zhou Zheng Li 

机构地区：[1]Department of Andrology,The Center for Men’s Health,Urologic Medical Center,Shanghai Key Laboratory of Reproductive Medicine,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [2]Department of Urology,The Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,China [3]Department of Interventional Medicine,Guangdong Provincial Key Laboratory of Biomedical Imaging,The Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai 519000,China [4]School of Life Science and Technology,ShanghaiTech University,Shanghai 200120,China

出　　处：《Asian Journal of Andrology》2023年第6期662-673,共12页亚洲男性学杂志（英文版）

基　　金：This work was supported by grants from the National Key R&D Program of China(2022YFC2702700);National Natural Science Foundation of China(82201756 and 82171597);China Postdoctoral Science Foundation(2021M703747);GuangDong Basic and Applied Basic Research Foundation(2021A1515111109)。

摘　　要：Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals.Among the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS patients.Further analysis showed that X-inactive-specific transcript(XIST),a key factor that inactivates one X chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli cells.The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes,and further disrupts their transcription pattern and cellular function.This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells.These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia.Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.

关 键 词：Klinefelter syndrome nonobstructive azoospermia Sertoli cell SPERMATOGENESIS X chromosome inactivation 

分 类 号：R697[医药卫生—泌尿科学]