Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation  

作　　者：Jian-Wu Shi Yi-Wen Zhou Yu-Fei Chen Mei Ye Feng Qiao Jia-Wei Tian Meng-Ya Zhang Hao-Cheng Lin Gang-Cai Xie Kin Lam Fok Hui Jiang Yang Liu Hao Chen 

机构地区：[1]Institute of Reproductive Medicine,Medical School of Nantong University,Nantong 226000,China [2]Department of Plastic and Reconstructive Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [3]Department of Urology,Peking University Third Hospital,Beijing 100191,China [4]School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China

出　　处：《Asian Journal of Andrology》2023年第1期103-112,共10页亚洲男性学杂志（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China (No.2018YFC1003602 to HC and No.2018YFC1003504 to HJ);the National Natural Science Foundation of China (No.81871202 to HC and No.31900484 to GCX);Lo Kwee Seong Start Up Fund to KLE,Shanghai Sailing Program (No.20YF1422900 to YWZ);the Natural Science Foundation of Nantong (No.JC2021081 to JWS);Startup R&D funding from Nantong University (No.135419631032 to JWS and TDYX2021021 to JWS).

摘　　要：This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)gene.Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1.The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development.The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis.Microfluidic-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically decreased.Bioinformatics analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(EMT)process.The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

关 键 词：disorders of sex development human epididymis NR5A1 scRNA-seq 

分 类 号：R697[医药卫生—泌尿科学]