Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling  

作　　者：Feifei Liu Yi Lu Xuebao Wang Shuhui Sun Huize Pan Min Wang Zehua Wang Weiqi Zhang Shuai Ma Guoqiang Sun Qun Chu Si Wang Jing Qu Guang-Hui Liu 

机构地区：[1]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [2]Sports Medicine Department,Beijing Jishuitan Hospital,Capital Medical University,Beijing 100035,China [3]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China [4]University of Chinese Academy of Sciences,Beijing 100049,China [5]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [6]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China [7]National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [8]Division of Life Sciences and Medicine,School of Life Sciences,University of Science and Technology of China,Hefei 230001,China [9]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [10]The Fifth People’s Hospital of Chongqing,Chongqing 400062,China [11]Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China [12]Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China

出　　处：《Protein & Cell》2024年第6期441-459,共19页蛋白质与细胞（英文版）

基　　金：supported by the National Natural Science Foundation of China(92149301,81921006,82125011);the National Key Research and Development Program of China(2022YFA1103700,2022YFA1103800,2020YFA0804000,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400);the National Natural Science Foundation of China(92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,32000500,82271600);CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012);the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310);Youth Innovation Promotion Association of CAS(E1CAZW0401,2023092,2022083);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);Excellent Young Talents Program of Capital Medical University(12300927);Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105);Young Elite Scientists Sponsorship Program by CAST(2021QNRC001).

摘　　要：The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

关 键 词：FOXO1 DEGENERATION inflammation 

分 类 号：R346[医药卫生—基础医学]