Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38107519", "kind": "science-record", "revision": 3, "content_hash": "sha256:5ee63ae6a5c505b32d8e3e8e32a3af56e821a900a0a79dbf833350f9487285df", "created_at": "2026-11-01T19:03:02Z", "updated_at": "2026-11-01T22:10:53Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers.", "doi": "10.3389/fendo.2023.1275612", "pmid": "38107519", "authors": ["Yangzhou Lu", "Xiaogang Liu", "Jingling Zhao", "Fan Bie", "Yiling Liu", "Julin Xie", "Peng Wang", "Junyou Zhu", "Yahui Xiong", "Shitian Qin", "Fan Yang", "Lei Chen", "Yingbin Xu"], "journal": "Frontiers in endocrinology", "year": 2023, "abstract": "Background: The treatment of diabetic foot ulcers (DFUs) poses a challenging medical problem that has long plagued individuals with diabetes. Clinically, wounds that fail to heal for more than 12 weeks after the formation of DFUs are referred to as non-healing/chronic wounds. Among various factors contributing to the non-healing of DFUs, the impairment of skin microvascular endothelial cell function caused by high glucose plays a crucial role. Our study aimed to reveal the transcriptomic signatures of non-healing DFUs endothelial cells, providing novel intervention targets for treatment strategies.\nMethods: Based on the GEO dataset (GSE165816), we selected DFU-Healer, DFU-Non-healer, and healthy non-diabetic controls as research subjects. Single-cell RNA transcriptomic sequencing technology was employed to analyze the heterogeneity of endothelial cells in different skin tissue samples and identify healing-related endothelial cell subpopulations. Immunofluorescence was applied to validate the sequencing results on clinical specimens.\nResults: The number of endothelial cells and vascular density showed no significant differences among the three groups of skin specimens. However, endothelial cells from non-healing DFUs exhibited apparent inhibition of angiogenesis, inflammation, and immune-related signaling pathways. The expression of CCND1, ENO1, HIF1α, and SERPINE1 was significantly downregulated at the transcriptomic and histological levels. Further analysis demonstrated that healing-related endothelial cell subpopulations in non-healing DFUs has limited connection with other cell types and weaker differentiation ability.\nConclusion: At the single-cell level, we uncovered the molecular and functional specificity of endothelial cells in non-healing DFUs and highlighted the importance of endothelial cell immune-mediated capability in angiogenesis and wound healing. This provides new insights for the treatment of DFUs.", "claims": [{"id": "claim-method", "statement": "The FindMarkers tool of the Seurat package was used to analyze differential gene expression in the sample cells.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38107519", "locator": "sections[4] \"Data processing and analysis\" paragraph 2", "quote": "The FindMarkers tool of the Seurat package was used to analyze differential gene expression in the sample cells."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE165816.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38107519", "locator": "sections[15] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE165816."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Across 25 samples and 53,199 cells, the study uncovered the molecular and functional specificity of endothelial cells in non-healing DFUs and highlighted the importance of endothelial-cell immune-mediated capability in angiogenesis and wound healing.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38107519", "locator": "sections[9] \"Identification and gene features of skin tissue cells\" paragraph 2", "quote": "We analyzed a total of 25 samples from 11 diabetes patients (7 DFU-Healers and 4 DFU-Non-Healers) and 10 healthy non-diabetic subjects."}, {"asset": "source:pmid:38107519", "locator": "sections[9] \"Identification and gene features of skin tissue cells\" paragraph 2", "quote": "In summary, following the cell type marker information provided in the research of Georgios Theocharidis et al. (14), we analyzed 53,199 cells (24,922 from normal skin, 12,173 from DFU-Healers, and 17,743 from DFU-Non-Healers) and created a gene expression matrix for each cell."}, {"asset": "source:pmid:38107519", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "At the single-cell level, we uncovered the molecular and functional specificity of endothelial cells in non-healing DFUs and highlighted the importance of endothelial cell immune-mediated capability in angiogenesis and wound healing."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Across 25 samples and 53,199 cells, the study uncovered the molecular and functional specificity of endothelial cells in non-healing DFUs and highlighted the importance of endothelial-cell immune-mediated capability in angiogenesis and wound healing.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38107519"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE165816"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE165816"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38107519", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2023.1275612", "sha256": "sha256:cb219ed4baa9ec6a2cab6ecb5bc09b266ad96f3fad9d9dec887905184733aa7d", "bytes": 71374, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2023.1275612", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10722230", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE165816", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE165816", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE165816", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Immunofluorescence was applied to validate the sequencing resul", "FU-Healer and DFU-Non Healer groups. (F) The immunofluorescence validation of protein expression, with CD31", "mpared to DFU-Healer (p<0.05) ( Figure 3E ). Immunofluorescence staining of CD31 in conjunction with CCND1,", "1Clinical details on skin tissue donors for immunofluorescence staining.Click here for additional data file"], "order_basis": "paper_text_order:1038", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["s project were extracted. 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