Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells
LiangYu Zhao,
ChenCheng Yao,
XiaoYu Xing,
Tao Jing,
Peng Li,
ZiJue Zhu,
Chao Yang,
Jing Zhai,
RuHui Tian,
HuiXing Chen,
JiaQiang Luo,
NaChuan Liu,
ZhiWen Deng,
XiaoHan Lin,
Na Li,
Jing Fang,
Jie Sun (),
ChenChen Wang (),
Zhi Zhou () and
Zheng Li ()
Additional contact information
LiangYu Zhao: Shanghai Jiao Tong University School of Medicine
ChenCheng Yao: Shanghai Jiao Tong University School of Medicine
XiaoYu Xing: Shanghai Jiao Tong University
Tao Jing: Shanghai Jiao Tong University School of Medicine
Peng Li: Shanghai Jiao Tong University School of Medicine
ZiJue Zhu: Shanghai Jiao Tong University School of Medicine
Chao Yang: Shanghai Jiao Tong University School of Medicine
Jing Zhai: Shanghai Jiao Tong University School of Medicine
RuHui Tian: Shanghai Jiao Tong University School of Medicine
HuiXing Chen: Shanghai Jiao Tong University School of Medicine
JiaQiang Luo: Shanghai Jiao Tong University School of Medicine
NaChuan Liu: Shanghai Jiao Tong University School of Medicine
ZhiWen Deng: ShanghaiTech University
XiaoHan Lin: ShanghaiTech University
Na Li: ShanghaiTech University
Jing Fang: ShanghaiTech University
Jie Sun: Shanghai Jiao Tong University
ChenChen Wang: Chinese Academy of Sciences
Zhi Zhou: ShanghaiTech University
Zheng Li: Shanghai Jiao Tong University School of Medicine
Nature Communications, 2020, vol. 11, issue 1, 1-15
Abstract:
Abstract 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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19414-4
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DOI: 10.1038/s41467-020-19414-4
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