A single-cell transcriptomic landscape of mouse testicular aging

Zhang, Wei1,2,3; Xia, Siyu1,2,3; Xiao, Wei4; Song, Yali5; Tang, Li5; Cao, Min1,2,3; Yang, Jing1,2,3; Wang, Shuang1,2,3; Li, Zhijie1,2,3; Xu, Chengchao1,2,3; Liu, Jianqiao6; Zhao, Shanchao7,8; Yang, Chuanbin1,2,3; Wang, Jigang1,2,3,5,9,10

2023-11-01

10.1016/j.jare.2022.12.007

JOURNAL OF ADVANCED RESEARCH   影响因子和分区

2090-1232

2090-1224

Introduction: Advanced paternal age of reproduction is an increasing trend, especially in developed coun-tries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fer-tility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging -associated molecular and cellular alterations in testicular tissue is still missing. Objectives: We aimed to dissect aging-associated molecular characteristics in testes of mice. Methods: Single-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to character-ize aging-associated phenotypes and verify single cell sequence results. Results: Here, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'in-flammation', which were major aging-associated characteristics. Further analysis of aging-related differ-entially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. Conclusion: Taken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type -specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Aging Testis Single-cell RNA sequencing Senescence Inflammation

SCI

英语

第一 ; 通讯

National Key Research and Devel- opment Program of China["2020YFA0908000","2022YFC2303600"] ; National Natural Science Foundation of China["82003721","82074098","82274182","81841001","82173914"] ; Shenzhen Science and Technology Innovation Commission["JCYJ20210324114014039","JCYJ20210324115800001","JCYJ20220818102613029"] ; Guangdong Basic and Applied Basic Research Foundation[2020A1515110549] ; Innovation Team and Talents Cultivation Program of National Administration of Tra[ZYYCXTD-C-202002] ; Guangdong- Dongguan Joint Fund Regional Cultivation Project[2021B1515140033] ; Dongguan Science and Technology of Social Development Program[20221800905732] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001102793100001

ELSEVIER

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Nephrol,Clin Med Coll 2, Shenzhen 518020, Peoples R China
2.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Shenzhen key Lab, Shenzhen 518020, Peoples R China
3.Shenzhen Peoples Hosp, Shenzhen Clin Res Ctr Geriatr, Shenzhen 518020, Peoples R China
4.Guangdong Pharmaceut Univ, Key Lab Glucolipid Metab Disorder, Minist Educ, Guangzhou 510006, Peoples R China
5.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Ctr Reprod Med, Dongguan 523000, Peoples R China
6.Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Reprod Med Guangdong Prov, Guangzhou 510150, Peoples R China
7.Southern Med Univ, Affiliated Hosp 3, Dept Urol, Guangzhou 510500, Peoples R China
8.Southern Med Univ, Nanfang Hosp, Guangzhou 510500, Peoples R China
9.China Acad Chinese Med Sci, Artemisinin Res Ctr, Beijing 100700, Peoples R China
10.Inst Chinese Mat Med, China Acad Chinese Med Sci, Beijing 100700, Peoples R China

Zhang, Wei,Xia, Siyu,Xiao, Wei,et al. A single-cell transcriptomic landscape of mouse testicular aging[J]. JOURNAL OF ADVANCED RESEARCH,2023,53.

Zhang, Wei.,Xia, Siyu.,Xiao, Wei.,Song, Yali.,Tang, Li.,...&Wang, Jigang.(2023).A single-cell transcriptomic landscape of mouse testicular aging.JOURNAL OF ADVANCED RESEARCH,53.

Zhang, Wei,et al."A single-cell transcriptomic landscape of mouse testicular aging".JOURNAL OF ADVANCED RESEARCH 53(2023).