{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:09:53Z","timestamp":1783940993906,"version":"3.55.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92149301"],"award-info":[{"award-number":["92149301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81921006"],"award-info":[{"award-number":["81921006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82125011"],"award-info":[{"award-number":["82125011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1103700"],"award-info":[{"award-number":["2022YFA1103700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1103800"],"award-info":[{"award-number":["2022YFA1103800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0804000"],"award-info":[{"award-number":["2020YFA0804000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0112200"],"award-info":[{"award-number":["2020YFA0112200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF1201000"],"award-info":[{"award-number":["2021YFF1201000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/procel\/pwad060","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T17:17:25Z","timestamp":1702401445000},"page":"441-459","source":"Crossref","is-referenced-by-count":24,"title":["Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling"],"prefix":"10.1093","volume":"15","author":[{"given":"Feifei","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Sports Medicine Department, Beijing Jishuitan Hospital, Capital Medical University , Beijing 100035 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huize","family":"Pan","sequence":"additional","affiliation":[{"name":"National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Division of Life Sciences and Medicine, School of Life Sciences, University of Science and Technology of China , Hefei 230001 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0906-9026","authenticated-orcid":false,"given":"Zehua","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8885-5104","authenticated-orcid":false,"given":"Weiqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , China"},{"name":"The Fifth People\u2019s Hospital of Chongqing , Chongqing 400062 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-0612","authenticated-orcid":false,"given":"Si","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fifth People\u2019s Hospital of Chongqing , Chongqing 400062 , China"},{"name":"Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University , Beijing 100053 , China"},{"name":"Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University , Beijing 100053 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3988-5067","authenticated-orcid":false,"given":"Jing","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"University of Chinese Academy of Sciences , Beijing 100049 , China"},{"name":"Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101 , China"},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine , Beijing 100101 , 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