Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells

Author:

Zhao LiangYu,Yao ChenCheng,Xing XiaoYu,Jing Tao,Li Peng,Zhu ZiJue,Yang Chao,Zhai Jing,Tian RuHui,Chen HuiXing,Luo JiaQiang,Liu NaChuan,Deng ZhiWen,Lin XiaoHan,Li Na,Fang Jing,Sun Jie,Wang ChenChen,Zhou Zhi,Li ZhengORCID

Abstract

AbstractClinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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