首页|Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular deter-minants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2high)characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2high accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

spatial transcriptomeprimateovaryagingsenescenceinflammation

Huifen Lu、Ying Jing、Chen Zhang、Shuai Ma、Weiqi Zhang、Daoyuan Huang、Bin Zhang、Yuesheng Zuo、Yingying Qin、Guang-Hui Liu、Yang Yu、Jing Qu、Si Wang

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Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China

Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China

The Fifth People's Hospital of Chongqing,Chongqing 400062,China

State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China

Institute for Stem cell and Regeneration,CAS,Beijing 100101,China

Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

Aging Biomarker Consortium,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100049,China

CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China

China National Center for Bioinformation,Beijing 100101,China

Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China

Sino-Danish Center for Education and Research,Beijing 101408,China

Aging Biomarker Consortium,Beijing 1001

Center for Reproductive Medicine,Cheeloo College of Medicine,Shandong University,Jinan 250012,China

Key Laboratory of Reproductive Endocrinology of Ministry of Education,National Research Center for Assisted Reproductive Technology and Reproductive Genetics,Shandong Key Laboratory of Reproductive Medicine,Shandong Provincial Clinical Research Center for Reproductive Health,Jinan 250012,China

University of Chinese Academy o

Department of Obstetrics and Gynecology,Center for Reproductive Medicine,Peking University,Third Hospital,Beijing 100191,China

Clinical Stem Cell Research Center,Peking University,Third Hospital,Beijing 100191,China

State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaSTI2030-Major ProjectsNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCAS Project for Young Scientists in Basic ResearchCAS Project for Young Scientists in Basic ResearchStrategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine,Ferring PharmaceuticalsChinese Academy of SciencesProgram of the Beijing Natural Science FoundationInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesNew Cornerstone Science Foundation through the XPLORER PRIZEYouth Innovation Promotion Association of CASYouth Innovation Promotion Association of CASExcellent Young Talents Program of Capital Medical UniversityProject for Technology Development of Beijingaffiliated Medical Research InstitutesExcellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher TeamYoung Elite Scientists Sponsorship Program by CASTFellowship of China Postdoctoral Science Foundation

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2024

10.1093/procel/pwad063

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(5)
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