RT Journal Article SR Electronic T1 Single-cell atlas of human developing and azoospermia patients’ testicles reveals the roadmap and defects in somatic microenvironment JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.07.082024 DO 10.1101/2020.05.07.082024 A1 LiangYu Zhao A1 ChenCheng Yao A1 XiaoYu Xing A1 Tao Jing A1 Peng Li A1 ZiJue Zhu A1 Chao Yang A1 Jing Zhai A1 RuHui Tian A1 HuiXing Chen A1 JiaQiang Luo A1 NaChuan Liu A1 ZhiWen Deng A1 XiaoHan Lin A1 Na Li A1 Jing Fang A1 Jie Sun A1 ChenChen Wang A1 Zhi Zhou A1 Zheng Li YR 2020 UL http://biorxiv.org/content/early/2020/05/08/2020.05.07.082024.abstract AB Non-obstructive azoospermia (NOA) affects 1% of men. However, the unknowns of NOA pathogenesis and even normal spermatogenic microenvironment establishment severely limit the clinical efficacy of NOA treatment. We profiled > 80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. Sertoli cells, which form the scaffold in the testicular microenvironment, exhibited the most obvious damages in NOA patients. We identified the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature but with abnormal immune response, while the cells in idiopathic NOA (iNOA) are basically physiologically immature. Furthermore, inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA.Competing Interest StatementThe authors have declared no competing interest.