Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

作     者：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 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

作者机构：Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine CenterInternational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane BiologyInstitute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China Beijing Institute for Stem Cell and Regenerative MedicineBeijing 100101China CAS Key Laboratory of Genomic and Precision MedicineBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and RegenerationCASBeijing 100101China China National Center for BioinformationBeijing 100101China The Fifth People’s Hospital of ChongqingChongqing 400062China Sino-Danish CollegeUniversity of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and ResearchBeijing 101408China Department of Obstetrics and GynecologyCenter for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research CenterPeking UniversityThird HospitalBeijing 100191China Center for Reproductive MedicineCheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker ConsortiumBeijing 100101China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2024年第15卷第5期

页      面：364-384页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071008[理学-发育生物学] 

基　　金：This work was supported by the National Natural Science Foundation of China(Grant Nos.82122024,92149301,82125011,81921006) the National Key Research and Development Program of China(2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400) the National Natural Science Foundation of China(Grant Nos.92168201,82225019,91949209,92049304,82071588,82322025,32000500,82271600,92049116,32121001,82192863,82201714) CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012) the Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine,Ferring Pharmaceuticals and the Chinese Academy of Sciences(FIRMC180305) the Program of the Beijing Natural Science Foundation(Z230011) the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101) New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045) Youth Innovation Promotion Association of CAS(2022083,E1CAZW0401) Excellent Young Talents Program of Capital Medical University(12300927) the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310) Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105) Young Elite Scientists Sponsorship Program by CAST(2021QNRC001) The Fellowship of China Postdoctoral Science Foundation(2022M712216) 

主　　题：spatial transcriptome primate ovary aging senescence inflammation 

摘      要：The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** 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 ***,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(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal *** 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.