Single-cell sequencing reveals the response mechanisms of vascular endothelial cells to glucocorticoids in diabetic retinopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41196918", "kind": "science-record", "revision": 4, "content_hash": "sha256:485f01e7d2c772fd47d489f921953fbdf9a2408a8efb8820ebb5625739d6ca6e", "created_at": "2026-11-01T20:31:14Z", "updated_at": "2026-11-01T22:57:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Single-cell sequencing reveals the response mechanisms of vascular endothelial cells to glucocorticoids in diabetic retinopathy.", "doi": "10.1371/journal.pone.0334230", "pmid": "41196918", "authors": ["Lingda Wang", "Rong Zhang", "Lin Wang", "Yongrui Wang", "Xiaodan Zhang", "Guohong Zhou"], "journal": "PloS one", "year": 2025, "abstract": "BACKGROUND: One serious consequence of diabetes mellitus is diabetic retinopathy (DR), which impairs eyesight to the point of blindness. While glucocorticoid medications are commonly employed in the management of DR, their therapeutic efficacy requires enhancement. Due to the tight association between glucocorticoid-related genes and the onset and development of DR, a comprehensive examination of its root cause of activity may be able to overcome the drawbacks of existing treatment approaches.\nMETHODS: R programming tools were used to examine the single-cell RNA sequencing (scRNA-seq) dataset GSE178121, which was obtained from the Gene Expression Omnibus (GEO) database. To evaluate glucocorticoid activity, a gene set related to glucocorticoid phenotypes was sourced from the Molecular Signatures Database (MSigDB), followed by the identification of key cellular populations within DR tissues. Subsequently, these key cells underwent pseudotime analysis, transcription factor (TF) evaluation, cell-cell communication assessment, differential gene screening, and the construction of a regulatory network.\nRESULTS: Our investigation demonstrated that vascular endothelial cells (VECs) in DR tissue exhibited markedly elevated glucocorticoid activity. KLF4 is among the TFs that are intimately linked to the onset of DR, and hydroxyurea could be a beneficial medication. Cell-cell communication analysis highlighted the PTN and ANGPTL signaling pathways as important signaling pathways in DR. In the meanwhile, we identified 25 Hub genes, including DUSP6, AP1S2, and PTPRB, which were verified to be differentially expressed in DR.\nCONCLUSION: In conclusion, our comprehensive study elucidated the complex interactions of glucocorticoids in the pathogenesis of DR, thereby revealing potential signaling pathways and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis between the identified key cells of the DR group and the Control group was conducted at the single-cell level. The “limma” R package was used to discover DEGs in those critical cells, with a selection criterion of |logFC| > 0.25 and P value < 0.05 for further investigation [13].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41196918", "locator": "sections[5] \"Analysis of cell differences between groups\" paragraph 2", "quote": "Differential expression analysis between the identified key cells of the DR group and the Control group was conducted at the single-cell level. The “limma” R package was used to discover DEGs in those critical cells, with a selection criterion of |logFC| > 0.25 and P value < 0.05 for further investigation [13]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the paper and its Supporting information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41196918", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the paper and its Supporting information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:41196918"], "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:GSE178121"], "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:GSE178121"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41196918", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0334230", "sha256": "sha256:3f82385916011e429088c2e1446073dc750e96886c692d63e1d1667f3c147f07", "bytes": 67474, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0334230", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12591416", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE178121", "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=GSE178121", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE178121", "version": null, "note": "All relevant data are within the paper and its Supporting information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All relevant data are within the paper and its Supporting information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5380581", "GSM5380582"], "sample_count": 2, "group_sizes": null, "group_sizes_basis": null, "platform": "24247", "taxon": "Mus musculus", "title": "Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE178121 not downloaded", "asset:data:geo:GSE178121 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differential expression analysis between the identified key cells of the DR group and the Control group was conducted at the single-cell level. 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