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Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation

摘要Lumbar disc(LD)herniation and aging are prevalent conditions that can result in substantial morbidity.This study aimed to clarify the mechanisms connecting the LD aging and herniation,particularly focusing on cellular senes-cence and molecular alterations in the nucleus pulposus(NP).We performed a detailed analysis of NP samples from a diverse cohort,including individuals of varying ages and those with diagnosed LD herniation.Our method-ology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molec-ular changes related to NP aging and herniation.We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells(NPPCs)are central to both processes.Additionally,we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD.This research offers fresh insights into LD aging and its associated pathologies,potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.

作者 Min Wang ^[1] Zan He ^[2] Anqi Wang ^[3] Shuhui Sun ^[4] Jiaming Li ^[5] Feifei Liu ^[6] Chunde Li ^[7] Chengxian Yang ^[7] Jinghui Lei ^[2] Yan Yu ^[8] Shuai Ma ^[9] Si Wang ^[10] Weiqi Zhang ^[11] Zhengrong Yu ^[7] Guang-Hui Liu ^[12] Jing Qu ^[13] 学术成果认领

作者单位 State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Division of Life Sciences and Medicine,School of Life Sciences,University of Science and Technology of China,Hefei 230001,China ^[1] 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,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China ^[2] Department of Orthopaedics,Peking University First Hospital,Beijing 100034,China;Department of Musculoskeletal Oncology,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China ^[3] State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;Beijing Institute of Heart Lung and Blood Vessel Diseases,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China ^[4] University of Chinese Academy of Sciences,Beijing 100049,China;China National Center for Bioinformation,Beijing 100101,China;Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China ^[5] Beijing Institute of Heart Lung and Blood Vessel Diseases,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China ^[6] Department of Orthopaedics,Peking University First Hospital,Beijing 100034,China ^[7] State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China ^[8] State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;Aging Biomarker Consortium,Beijing 100101,China ^[9] 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,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Aging Biomarker Consortium,Beijing 100101,China ^[10] University of Chinese Academy of Sciences,Beijing 100049,China;China National Center for Bioinformation,Beijing 100101,China;Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;Aging Biomarker Consortium,Beijing 100101,China ^[11] State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;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,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;University of Chinese Academy of Sciences,Beijing 100049,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;Aging Biomarker Consortium,Beijing 100101,China ^[12] State Key Laboratory of Organ Regeneration and Reconstruction,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;Beijing Institute of Heart Lung and Blood Vessel Diseases,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Aging Biomarker Consortium,Beijing 100101,China ^[13]

关键词 aging herniation nucleus pulposus single-nucleus transcriptomics NFAT1 senescence

栏目名称

RESEARCH ARTICLES

DOI 10.1093/procel/pwaf025

发布时间 2025-09-12（万方平台首次上网日期，不代表论文的发表时间）

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