{"doi":"10.1038/s42003-025-08586-8","title":"A multi-tissue human knee single-cell atlas identifies that osteoarthritis reduces regenerative tissue stem cells while increasing inflammatory pain macrophages","abstract":"Osteoarthritis (OA) affects the entire knee joint, yet cross-tissue molecular interplay remains poorly understood. To address this, we constructed the first single-cell RNA sequencing atlas of knee OA, profiling articular cartilage, meniscus, synovium, and subchondral bone. Our analysis revealed that healthy synovium and meniscus harbor abundant tissue stem cells (TSCs) and immune cells, which are significantly altered in OA. Regenerative TSCs expressing SDF1, SOX9, CD146, PDGFRB, and CD105 are reduced, while osteogenic TSCs marked by NT5E are expanded. OA cartilage has distinct MMP13-producing detrimental chondrocytes while increasing RUNX2-producing chondrocytes and fibroblasts. OA tissues are enriched with inflammatory (IL1B-IL6-NOS2-TNF) and pain-marker (P2RX7)-specific macrophages, inflammatory genes expression and immune cells. Cell-cell communication contributes to OA progression, promotes proinflammatory macrophages, and osteogenic TSCs. By identifying these OA-specific cells and molecular interplay, and constructing the first multi-tissue comprehensive atlas, we bridge the critical knowledge gaps and lay the foundation for advancing targeted OA therapies. Comprehensive multi-tissue single-cell atlas of human knee osteoarthritis reveals distinct chondrocytes, inflammatory macrophages, osteogenic stem cells, and synovial fibroblasts offering critical insights into mechanisms and therapies.","journal":"Communications Biology","year":2025,"id":510862,"datarank":0.4684276838633119,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.026761836988345757,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.026761836988345757,"corpus_percentile":59.441479074804676,"corpus_rank":5244,"citation_count":18,"citer_count":17,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":37.5,"fair_percentile":50.687863038826045,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1368026,"name":"Amit Kumar Chakraborty","orcid":"0000-0001-7455-6579","position":1,"is_corresponding":false},{"id":55625,"name":"Tuhina Neogi","orcid":"0000-0002-9515-1711","position":2,"is_corresponding":false},{"id":1133474,"name":"Michael B. Albro","orcid":"0000-0002-3071-0252","position":3,"is_corresponding":false},{"id":399141,"name":"Brian D. Snyder","orcid":"0000-0003-1482-9509","position":4,"is_corresponding":false},{"id":456215,"name":"Thomas P. Schaer","orcid":"0000-0002-4340-8212","position":5,"is_corresponding":false},{"id":291179,"name":"Chao Zhang","orcid":"0000-0001-8019-7998","position":6,"is_corresponding":false},{"id":290956,"name":"Mark W. Grinstaff","orcid":"0000-0002-5453-3668","position":7,"is_corresponding":false},{"id":411954,"name":"Manish V. Bais","orcid":"0000-0003-4198-7377","position":8,"is_corresponding":false},{"id":1368025,"name":"Rajnikant Raut","orcid":"0000-0001-6963-5889","position":0,"is_corresponding":true}],"reference_count":127,"raw_metadata":null,"created_at":"2026-07-19T02:47:50.575618Z","pmid":"40753276","pmcid":"PMC12317986","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":55.5556,"fair_a":37.5,"fair_i":0.0,"fair_r":25.0,"fair_zscore":0.1208,"fair_rationale":{"fair_score":37.5,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":55.56,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","grounded":false,"rationale":"GEO accession numbers (GSE series) are persistent identifiers in the repository scheme list. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (4/5 passes agreed)]","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"samples of cartilage, meniscus, synovium & infrapatellar fat pad (SynoFP), and SCB from healthy individuals and OA patients were collected from the NCBI Gene Expression Omnibus (GEO) database","grounded":true,"rationale":"The paper names NCBI GEO as the repository from which the data were collected and where they are publicly available. 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[downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","grounded":false,"rationale":"The data are openly accessible from GEO with no named gatekeeper, so no institutional or personal gatekeeper is identified.","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","grounded":false,"rationale":"The data are stated to be publicly available now, but no statement about how long they will persist (retention period) is given. [downgraded to 'no' — no verifiable quote from the paper]","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format is named for the released data.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No community standard (e.g., MIAME, MINSEQE, ontology) is named for the data or metadata.","anchors":["RDA-R1.3-01M — 'Metadata complies with a community standard' (priority Essential)","RDA-R1.3-01D — 'Data complies with a community standard'","RDA-I2-01M — '(Meta)data use vocabularies that follow FAIR principles'"],"scored":false,"signal":null},{"key":"i_qualified_references","label":"Identifiers for the resources the data depend on","kind":"llm","weight":0.5,"fraction":0.0,"verdict":"no","evidence":"GSE220243, GSE169454, GSE255460, GSE216651, GSE196678","grounded":false,"rationale":"The paper gives GEO accession identifiers for the source datasets used in the study, which are resources other than the paper's own dataset. 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'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No licence is stated for the data; the article's CC-BY-NC-ND licence applies to the paper, not the data.","gain":16.67,"priority":"essential","scored":true},{"key":"f_dataset_pid","dimension":"F","label":"Persistent identifier for the data","action":"Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","why":"GEO accession numbers (GSE series) are persistent identifiers in the repository scheme list. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (4/5 passes agreed)]","gain":8.33,"priority":"essential","scored":true},{"key":"a_data_openly_accessible","dimension":"A","label":"Access route free of preconditions","action":"Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","why":"The route to the data is given with no stated precondition (publicly available in GEO). [downgraded to 'partial' — no verifiable quote from the paper]","gain":8.33,"priority":"essential","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. 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[majority verdict 'no' (3/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"a_controlled_access_for_sensitive","dimension":"A","label":"Gatekeeper for sensitive data","action":"Route sensitive data through an institutional gatekeeper — deposit in a controlled- access repository (dbGaP, EGA) with a Data Access Committee and a published DUA — rather than through the corresponding author's inbox. An author-gated dataset dies with the author's email address, and 'on reasonable request' has been shown repeatedly not to yield data. For sensitive/human genomics / sequencing data, use a controlled-access repository such as dbGaP or EGA.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","why":"The data are openly accessible from GEO with no named gatekeeper, so no institutional or personal gatekeeper is identified.","gain":0.0,"priority":"useful","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"GSE220243, GSE169454, GSE255460, GSE216651, GSE196678","why":"The paper gives GEO accession identifiers for the source datasets used in the study, which are resources other than the paper's own dataset. [downgraded to 'no' — no verifiable quote from the paper] [majority verdict 'no' (4/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":"The human knee OA single-cell RNA-seq data used in this study are publicly available under the following accession ID: cartilage (GSE220243, GSE169454, and GSE255460); meniscus (GSE220243); synovium and IPFP (GSE216651); and SCB (GSE196678).","why":"The data are stated to be publicly available now, but no statement about how long they will persist (retention period) is given. [downgraded to 'no' — no verifiable quote from the paper]","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Mint or cite a persistent identifier for the dataset — a repository DOI or an accession from a registered repository — and print it in the paper. A bare URL is not persistent: it is the single most common cause of a dead data link five years after publication. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For genomics / sequencing data, deposit in GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA).","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the genomics / sequencing repository accession (e.g. from GEO (GSE accession), SRA (SRP/SRR) or ENA/BioProject (PRJEB/PRJNA)) in the reference list.","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable. Prefer open genomics / sequencing formats such as FASTQ, BAM or VCF."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"unpaywall_pdf"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"unpaywall_pdf","fair_has_llm":true,"fair_computed_at":"2026-07-20T11:56:45.577654Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}