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.
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)。
