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 

机构地区：[1]Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [3]Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China [4]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [5]University of Chinese Academy of Sciences,Beijing 100049,China [6]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [7]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China [8]Institute for Stem cell and Regeneration,CAS,Beijing 100101,China [9]China National Center for Bioinformation,Beijing 100101,China [10]The Fifth People’s Hospital of Chongqing,Chongqing 400062,China [11]Sino-Danish College,University of Chinese Academy of Sciences,Beijing 101408,China [12]Sino-Danish Center for Education and Research,Beijing 101408,China [13]Department of Obstetrics and Gynecology,Center for Reproductive Medicine,Peking University,Third Hospital,Beijing 100191,China [14]Clinical Stem Cell Research Center,Peking University,Third Hospital,Beijing 100191,China [15]Center for Reproductive Medicine,Cheeloo College of Medicine,Shandong University,Jinan 250012,China [16]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 [17]Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [18]Aging Biomarker Cons

出　　处：《Protein & Cell》2024年第5期364-384,共21页蛋白质与细胞（英文版）

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).

摘　　要：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 determinants 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(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)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.

关 键 词：spatial transcriptome PRIMATE OVARY AGING SENESCENCE inflammation 

分 类 号：R339.38[医药卫生—人体生理学]