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

Min WANG; Zan HE; Anqi WANG; Shuhui SUN; Jiaming LI; Feifei LIU; Chunde LI; Chengxian YANG; Jinghui LEI; Yan YU; Shuai MA; Si WANG; Weiqi ZHANG; Zhengrong YU; Guang-Hui LIU; Jing QU

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

Author: Min WANG ¹ ; Zan HE ² ; Anqi WANG ³ ; Shuhui SUN ¹ ; Jiaming LI ⁴ ; Feifei LIU ⁵ ; Chunde LI ³ ; Chengxian YANG ³ ; Jinghui LEI ² ; Yan YU ¹ ; Shuai MA ¹ ; Si WANG ² ; Weiqi ZHANG ⁴ ; Zhengrong YU ³ ; Guang-Hui LIU ¹ ; Jing QU ¹
Author Information

1. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
2. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
3. Department of Orthopaedics, Peking University First Hospital, Beijing 100034, China.
4. University of Chinese Academy of Sciences, Beijing 100049, China.
5. Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Publication Type:Journal Article
Keywords: NFAT1; aging; herniation; nucleus pulposus; senescence; single-nucleus transcriptomics
MeSH: Intervertebral Disc Displacement/metabolism*; Humans; Aging/pathology*; Nucleus Pulposus/pathology*; Male; Female; Transcriptome; Middle Aged; Lumbar Vertebrae/pathology*; Adult; Cellular Senescence; Stem Cells/pathology*; Aged; Intervertebral Disc Degeneration/metabolism*
From: Protein & Cell 2025;16(8):667-684
CountryChina
Language:English
Abstract: 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 senescence 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 methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular 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.