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These authors contributed equally: LY Zhao, CC Yao, XY Xing, T Jing. The original version of this Article contained an error in figure legend 2f, which incorrectly read '(f) Immunofluorescence co-staining of GATA4 (green) with JUN (red, upper panel), ENO1 (red, middle panel), and DEFB119 (red, lower panel) in human testicular paraffin sections at three ages.'. The correct version states '(f) Immunofluorescence co-staining of GATA4 (red) with JUN (green, upper panel), ENO1 (green, middle panel), and DEFB119 (green, lower panel) in human testicular paraffin sections at three ages.'. This has been corrected in both the PDF and HTML versions of the Article. [Extracted from the article]

Clinical 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. Non-obstructive azoospermia affects 1% of men. Here, authors perform single-cell transcriptomic analysis of human testicular cells from healthy donors and non-obstructive azoospermia patients and find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from patients. [ABSTRACT FROM AUTHOR]