Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation Shi JW, Zhou YW, Chen YF, Ye M, Qiao F, Tian JW, Zhang MY, Lin HC, Xie GC, Fok KL, Jiang H, Liu Y, Chen H,

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Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation Jian-Wu Shi¹, Yi-Wen Zhou², Yu-Fei Chen¹, Mei Ye¹, Feng Qiao¹, Jia-Wei Tian¹, Meng-Ya Zhang¹, Hao-Cheng Lin³, Gang-Cai Xie¹, Kin Lam Fok⁴, Hui Jiang³, Yang Liu², Hao Chen¹ 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 Correspondence Address: Hao Chen, Institute of Reproductive Medicine, Medical School of Nantong University, Nantong 226000 China Yang Liu, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 China Source of Support: None, Conflict of Interest: None DOI: 10.4103/aja202226

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.


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    -  Shi JW
    -  Zhou YW
    -  Chen YF
    -  Ye M
    -  Qiao F
    -  Tian JW
    -  Zhang MY
    -  Lin HC
    -  Xie GC
    -  Fok KL
    -  Jiang H
    -  Liu Y
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