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A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis
Protein & Cell ; (12): 888-907, 2023.
Article ي En | WPRIM | ID: wpr-1010764
المكتبة المسؤولة: WPRO
ABSTRACT
The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
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النص الكامل: 1 الفهرس: WPRIM الموضوع الرئيسي: Primates / Sertoli Cells / Spermatogenesis / Stem Cells / Testis / Aging / Transcriptome المحددات: Animals اللغة: En مجلة: Protein & Cell السنة: 2023 نوع: Article
النص الكامل: 1 الفهرس: WPRIM الموضوع الرئيسي: Primates / Sertoli Cells / Spermatogenesis / Stem Cells / Testis / Aging / Transcriptome المحددات: Animals اللغة: En مجلة: Protein & Cell السنة: 2023 نوع: Article