{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:34:39Z","timestamp":1786120479737,"version":"build-2736575974"},"reference-count":50,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100018916","name":"Suzhou Municipal Health Commission","doi-asserted-by":"publisher","award":["SZZJ2023BAa20017"],"award-info":[{"award-number":["SZZJ2023BAa20017"]}],"id":[{"id":"10.13039\/100018916","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.fct.2026.116275","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:39:59Z","timestamp":1784536799000},"page":"116275","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Integrative single-cell transcriptomics and Mendelian randomization prioritize FN1 and DCN in intervertebral disc degeneration"],"prefix":"10.1016","volume":"216","author":[{"given":"Zhen","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9332-0418","authenticated-orcid":false,"given":"Wei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib1","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1007\/s10067-025-07606-6","article-title":"Multi-omics identification of circulating protein biomarkers for intervertebral disc degeneration using Mendelian randomization and scRNA-seq","volume":"44","author":"Bai","year":"2025","journal-title":"Clin. Rheumatol."},{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib2","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.3390\/ijms22094917","article-title":"The cellular composition of bovine coccygeal intervertebral discs: a comprehensive single-cell RNA-seq analysis","volume":"22","author":"Calio","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.fct.2026.116275_bib3","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/2166817","article-title":"The role of oxidative stress in intervertebral disc degeneration","volume":"2022","author":"Cao","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13075-021-02690-w","article-title":"Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation","volume":"24","author":"Castro","year":"2022","journal-title":"Arthritis Res. Ther."},{"issue":"7","key":"10.1016\/j.fct.2026.116275_bib5","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.3390\/ijms23073993","article-title":"Single-cell RNA-seq analysis of cells from degenerating and non-degenerating intervertebral discs from the same individual reveals new biomarkers for intervertebral disc degeneration","volume":"23","author":"Cherif","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2025.114691","article-title":"Single-cell RNA sequencing reveals shifts in cell maturity and function of endogenous and infiltrating cell types in response to acute intervertebral disc injury","volume":"451","author":"Clayton","year":"2025","journal-title":"Exp. Cell Res."},{"issue":"12","key":"10.1016\/j.fct.2026.116275_bib7","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.3390\/ijms23126460","article-title":"Recent advances in managing spinal intervertebral disc degeneration","volume":"23","author":"Costachescu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib8","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3390\/cells10092443","article-title":"Fibronectin: molecular structure, fibrillar structure and mechanochemical signaling","volume":"10","author":"Dalton","year":"2021","journal-title":"Cells"},{"issue":"2","key":"10.1016\/j.fct.2026.116275_bib9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41587-021-01033-z","article-title":"Differential abundance testing on single-cell data using k-nearest neighbor graphs","volume":"40","author":"Dann","year":"2022","journal-title":"Nat. Biotechnol."},{"issue":"7","key":"10.1016\/j.fct.2026.116275_bib10","doi-asserted-by":"crossref","first-page":"10703","DOI":"10.18632\/aging.202850","article-title":"ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration","volume":"13","author":"Ding","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.fct.2026.116275_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.774316","article-title":"The preventive effect of decorin on epidural fibrosis and epidural adhesions after laminectomy","volume":"12","author":"Ding","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib12","doi-asserted-by":"crossref","DOI":"10.1002\/jsp2.1231","article-title":"Intervertebral disc degeneration and how it leads to low back pain","volume":"6","author":"Diwan","year":"2023","journal-title":"JOR Spine"},{"key":"10.1016\/j.fct.2026.116275_bib13","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/1283383","article-title":"The role of decorin in autoimmune and inflammatory diseases","volume":"2022","author":"Dong","year":"2022","journal-title":"J. Immunol. Res."},{"key":"10.1016\/j.fct.2026.116275_bib14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13075-025-03489-9","article-title":"Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration","volume":"27","author":"Dube","year":"2025","journal-title":"Arthritis Res. Ther."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-021-00713-z","article-title":"A new immunometabolic perspective of intervertebral disc degeneration","volume":"18","author":"Francisco","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41413-021-00163-z","article-title":"Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs","volume":"9","author":"Gan","year":"2021","journal-title":"Bone Res."},{"issue":"6","key":"10.1016\/j.fct.2026.116275_bib17","doi-asserted-by":"crossref","first-page":"e316","DOI":"10.1016\/S2665-9913(23)00098-X","article-title":"Global, regional, and national burden of low back pain, 1990-2020, its attributable risk factors, and projections to 2050: a systematic analysis of the global burden of disease study 2021","volume":"5","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"10.1016\/j.fct.2026.116275_bib18","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.824771","article-title":"Single-cell RNA sequencing of the nucleus pulposus reveals chondrocyte differentiation and regulation in intervertebral disc degeneration","volume":"10","author":"Han","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"issue":"10","key":"10.1016\/j.fct.2026.116275_bib19","doi-asserted-by":"crossref","DOI":"10.1002\/jbm4.10675","article-title":"A guide for understanding and designing Mendelian randomization studies in the musculoskeletal field","volume":"6","author":"Hartley","year":"2022","journal-title":"JBMR Plus"},{"key":"10.1016\/j.fct.2026.116275_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115224","article-title":"Single-cell sequencing: new insights for intervertebral disc degeneration","volume":"165","author":"Hu","year":"2023","journal-title":"Biomed. Pharmacother."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib21","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-78675-x","article-title":"Single-cell sequencing reveals cellular heterogeneity of nucleus pulposus in intervertebral disc degeneration","volume":"14","author":"Jia","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.fct.2026.116275_bib22","article-title":"Single-cell RNA sequencing reveals differences in human normal and degenerative nucleus pulposus tissue profiles and cellular interactions","volume":"10","author":"Li","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"issue":"6","key":"10.1016\/j.fct.2026.116275_bib23","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.70370","article-title":"Single nuclear-spatial transcriptomic sequencing reveals distinct puncture-induced cell subpopulations in the intervertebral disc of a rat model","volume":"15","author":"Liang","year":"2025","journal-title":"Clin. Transl. Med."},{"issue":"10","key":"10.1016\/j.fct.2026.116275_bib24","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13464","article-title":"Spatially multicellular variability of intervertebral disc degeneration by comparative single-cell analysis","volume":"56","author":"Lin","year":"2023","journal-title":"Cell Prolif."},{"key":"10.1016\/j.fct.2026.116275_bib25","article-title":"Single-cell RNA-seq analysis reveals macrophage involvement in the progression of human intervertebral disc degeneration","volume":"9","author":"Ling","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.fct.2026.116275_bib26","first-page":"274","article-title":"Multiple nano-drug delivery systems for intervertebral disc degeneration: current status and future perspectives","volume":"23","author":"Liu","year":"2023","journal-title":"Bioact. Mater."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3390\/ijms24010208","article-title":"Discogenic low back pain: anatomy, pathophysiology and treatments of intervertebral disc degeneration","volume":"24","author":"Mohd Isa","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"10.1016\/j.fct.2026.116275_bib28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/jor.25670","article-title":"Fibronectin sensitizes activation of contractility, YAP, and NF-kappaB in nucleus pulposus cells","volume":"42","author":"Naha","year":"2024","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.fct.2026.116275_bib29","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jot.2025.06.003","article-title":"Regenerative strategies for intervertebral disc degeneration","volume":"53","author":"Ogaili","year":"2025","journal-title":"J Orthop Translat"},{"issue":"11","key":"10.1016\/j.fct.2026.116275_bib30","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202101149R","article-title":"Single-cell RNA-sequencing atlas of bovine caudal intervertebral discs: discovery of heterogeneous cell populations with distinct roles in homeostasis","volume":"35","author":"Panebianco","year":"2021","journal-title":"FASEB J."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s00586-024-08551-9","article-title":"Causal effects of plasma proteome on intervertebral disc degeneration: a comprehensive Mendelian randomization study","volume":"34","author":"Ren","year":"2025","journal-title":"Eur. Spine J."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib32","article-title":"Single-cell RNA sequencing reveals the differentiation and regulation of endplate cells in human intervertebral disc degeneration","volume":"14","author":"Shi","year":"2024","journal-title":"Sci. Rep."},{"issue":"16","key":"10.1016\/j.fct.2026.116275_bib33","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA"},{"key":"10.1016\/j.fct.2026.116275_bib34","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1038\/s41467-021-25960-2","article-title":"Confronting false discoveries in single-cell differential expression","volume":"12","author":"Squair","year":"2021","journal-title":"Nat. Commun."},{"issue":"12","key":"10.1016\/j.fct.2026.116275_bib35","doi-asserted-by":"crossref","first-page":"6612","DOI":"10.3390\/ijms23126612","article-title":"Current perspectives on nucleus pulposus fibrosis in disc degeneration and repair","volume":"23","author":"Sun","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"17","key":"10.1016\/j.fct.2026.116275_bib36","article-title":"Shared and compartment-specific processes in nucleus pulposus and annulus fibrosus during intervertebral disc degeneration","volume":"11","author":"Swahn","year":"2024","journal-title":"Adv. Sci. (Weinh.)"},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib37","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s43556-022-00109-9","article-title":"TGF-beta signal transduction: biology, function and therapy for diseases","volume":"3","author":"Tie","year":"2022","journal-title":"Mol Biomed"},{"issue":"5","key":"10.1016\/j.fct.2026.116275_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2023.106692","article-title":"Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration","volume":"26","author":"Wang","year":"2023","journal-title":"iScience"},{"issue":"12","key":"10.1016\/j.fct.2026.116275_bib40","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.18492","article-title":"Identifying the protective effects of the miR-874-3p\/ATF3 axis in intervertebral disc degeneration by single-cell RNA sequencing and validation","volume":"28","author":"Wang","year":"2024","journal-title":"J. Cell Mol. Med."},{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib38","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13448","article-title":"Oxidative stress in intervertebral disc degeneration: molecular mechanisms, pathogenesis and treatment","volume":"56","author":"Wang","year":"2023","journal-title":"Cell Prolif."},{"issue":"3","key":"10.1016\/j.fct.2026.116275_bib41","doi-asserted-by":"crossref","DOI":"10.1002\/jsp2.1349","article-title":"Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: a Mendelian randomization study","volume":"7","author":"Xu","year":"2024","journal-title":"JOR Spine"},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib42","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12967-025-06231-w","article-title":"FSTL1 accelerates nucleus pulposus-derived mesenchymal stem cell apoptosis in intervertebral disc degeneration by activating TGF-beta-mediated Smad2\/3 phosphorylation","volume":"23","author":"Yan","year":"2025","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.fct.2026.116275_bib43","first-page":"564","article-title":"Single-cell RNA sequencing-guided engineering of mitochondrial therapies for intervertebral disc degeneration by regulating mtDNA\/SPARC-STING signaling","volume":"48","author":"Yang","year":"2025","journal-title":"Bioact. Mater."},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib44","doi-asserted-by":"crossref","DOI":"10.1002\/jsp2.1196","article-title":"The involvement of immune system in intervertebral disc herniation and degeneration","volume":"5","author":"Ye","year":"2022","journal-title":"JOR Spine"},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.spinee.2024.09.011","article-title":"Combined single-cell RNA sequencing and Mendelian randomization to identify biomarkers associated with necrotic apoptosis in intervertebral disc degeneration","volume":"25","author":"Ye","year":"2025","journal-title":"Spine J."},{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib46","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.joca.2021.06.010","article-title":"Single-cell RNA-seq analysis identifies unique chondrocyte subsets and reveals involvement of ferroptosis in human intervertebral disc degeneration","volume":"29","author":"Zhang","year":"2021","journal-title":"Osteoarthr. Cartil."},{"issue":"9","key":"10.1016\/j.fct.2026.116275_bib47","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41590-023-01588-w","article-title":"Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets","volume":"24","author":"Zhao","year":"2023","journal-title":"Nat. Immunol."},{"issue":"6","key":"10.1016\/j.fct.2026.116275_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.slast.2024.100223","article-title":"A novel multi-omics approach for identifying key genes in intervertebral disc degeneration","volume":"29","author":"Zhao","year":"2024","journal-title":"SLAS Technol"},{"issue":"21","key":"10.1016\/j.fct.2026.116275_bib49","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.177789","article-title":"S1P regulates intervertebral disc aging by mediating endoplasmic reticulum-mitochondrial calcium ion homeostasis","volume":"9","author":"Zheng","year":"2024","journal-title":"JCI Insight"},{"issue":"1","key":"10.1016\/j.fct.2026.116275_bib50","doi-asserted-by":"crossref","DOI":"10.1002\/jsp2.1289","article-title":"Understanding the etiopathogenesis of lumbar intervertebral disc herniation: from clinical evidence to basic scientific research","volume":"7","author":"Zhou","year":"2024","journal-title":"JOR Spine"}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691526003492?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691526003492?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T22:31:08Z","timestamp":1786055468000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691526003492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":50,"alternative-id":["S0278691526003492"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2026.116275","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrative single-cell transcriptomics and Mendelian randomization prioritize FN1 and DCN in intervertebral disc degeneration","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2026.116275","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"116275"}}