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pmid:38195709

Biomarkers of UVB radiation-related senescent fibroblasts.

Mingyue Qiang · Zijia Dai

Scientific reports · 2024 doi:10.1038/s41598-023-51058-4

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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pmid:38195709
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title
Biomarkers of UVB radiation-related senescent fibroblasts.
doi
10.1038/s41598-023-51058-4
pmid
38195709
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[0]
Mingyue Qiang
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Zijia Dai
journal
Scientific reports
year
2024
abstract
Excessive exposure to ultraviolet (UV) light is known to induce photoaging in the skin, necessitating the development of effective anti-photoaging strategies to mitigate the adverse effects of UV radiation. Understanding the biofunctional characteristics of diverse skin cell types and unraveling the molecular modifications implicated in the aging process are pivotal in comprehending the intricacies of photoaging in human skin. Such insights are essential for paving the way for innovative interventions to counteract the deleterious impact of UV radiation on the skin. The single-cell RNA sequencing data of UVB-irradiated and normal control mouse skin in GSE173385 were downloaded from the Gene Expression Omniniub (GEO) database. First, cell types were identified using Seurat for normalization, dimensionality reduction and clustering. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were executed on these cell subpopulations. Using FindAllMarkers in the Seurat package to identify differential gene expression and Monocle2 cell trajectory analysis, we screened out hub genes related to the development trajectory of senescent fibroblasts during photoaging, and then combined it with 307 aging-related genes collected in the HAGR library, we finally identified two biomarkers. The efficiency of biomarkers in diagnosing UV radiation photoaging was also evaluated in the dataset. Concurrently, the immune infiltration of identified biomarkers under UV radiation has also been further explored. Moreover, we employed the Enrichr platform to conduct a comprehensive screening of drug molecules associated with the identified biomarkers. Our comprehensive analysis, employing Seurat for normalization, dimensionality reduction, and clustering, successfully identified ten distinct cell types within the samples. Then GO functional enrichment analysis showed that senescent fibroblasts are mainly involved in the regulation of immune effector processes such as cytokine-mediated signaling pathways, regulation of epithelial cell proliferation and intercellular adhesion. Afterwards, KEGG analysis determined the main biological pathways are: IL-17 signaling pathway, Cytokine-cytokine receptor interaction, Metabolism of xenobiotics by cytochrome P450. After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging. Meanwhile, the immune infiltration further implied that the expression of these two biomarkers was significantly correlated with immune cells. In addition, the Enrichr platform was used to screen the drug molecules related to these biomarkers. This strategic approach aimed to pinpoint effective molecular targets for the prevention and treatment of photoaging. Our investigation has effectively characterized biomarkers associated with fibroblast senescence during photoaging at the single-cell level, We have validated their correlation with cellular immune inflammation and identified potential drug targets through the utilization of the Enrichr platform. This foundational research establishes a robust basis for the development of therapeutic interventions targeting skin diseases resulting from photoaging.
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A comparison of untreated and UVB-treated skin samples was conducted by Student's t-test in order to locate the differentially expressed genes (DEGs).
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The datasets analysed during the current study are available in the [GEO] repository. [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173385]. Users can download relevant data for free for research and publish relevant articles.
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After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging.
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After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging.
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After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging.
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Single-cell RNA-seq of UVB-radiated Skin Reveals Landscape of Photoaging-related Inflammation and Protection by Vitamin D
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Complete file
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Understanding the biofunctional characteristics of diverse skin cell types and unraveling the molecular modifications implicated in the aging process are pivotal in comprehending the intricacies of photoaging in human skin. Such insights are essential for paving the way for innovative interventions to counteract the deleterious impact of UV radiation on the skin. The single-cell RNA sequencing data of UVB-irradiated and normal control mouse skin in GSE173385 were downloaded from the Gene Expression Omniniub (GEO) database. First, cell types were identified using Seurat for normalization, dimensionality reduction and clustering. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were executed on these cell subpopulations. Using FindAllMarkers in the Seurat package to identify differential gene expression and Monocle2 cell trajectory analysis, we screened out hub genes related to the development trajectory of senescent fibroblasts during photoaging, and then combined it with 307 aging-related genes collected in the HAGR library, we finally identified two biomarkers. The efficiency of biomarkers in diagnosing UV radiation photoaging was also evaluated in the dataset. Concurrently, the immune infiltration of identified biomarkers under UV radiation has also been further explored. Moreover, we employed the Enrichr platform to conduct a comprehensive screening of drug molecules associated with the identified biomarkers. Our comprehensive analysis, employing Seurat for normalization, dimensionality reduction, and clustering, successfully identified ten distinct cell types within the samples. Then GO functional enrichment analysis showed that senescent fibroblasts are mainly involved in the regulation of immune effector processes such as cytokine-mediated signaling pathways, regulation of epithelial cell proliferation and intercellular adhesion. Afterwards, KEGG analysis determined the main biological pathways are: IL-17 signaling pathway, Cytokine-cytokine receptor interaction, Metabolism of xenobiotics by cytochrome P450. After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging. Meanwhile, the immune infiltration further implied that the expression of these two biomarkers was significantly correlated with immune cells. In addition, the Enrichr platform was used to screen the drug molecules related to these biomarkers. This strategic approach aimed to pinpoint effective molecular targets for the prevention and treatment of photoaging. Our investigation has effectively characterized biomarkers associated with fibroblast senescence during photoaging at the single-cell level, We have validated their correlation with cellular immune inflammation and identified potential drug targets through the utilization of the Enrichr platform. This foundational research establishes a robust basis for the development of therapeutic interventions targeting skin diseases resulting from photoaging.", "claims": [{"id": "claim-method", "statement": "A comparison of untreated and UVB-treated skin samples was conducted by Student's t-test in order to locate the differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38195709", "locator": "sections[10] \"Analysis of the hub gene's expression by GSE41078 and GSE54413 datasets\" paragraph 2", "quote": "A comparison of untreated and UVB-treated skin samples was conducted by Student's t-test in order to locate the differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the [GEO] repository. [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173385]. 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Users can download relevant data for free for research and publish relevant articles."}], "state": "complete"}, {"id": "claim-target-result", "statement": "After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38195709", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "After differential gene expression and Monocle2 cell trajectory analysis, we matched the obtained hub genes with the aging-related genes collected in the HAGR library, and finally screened out two relevant biomarkers: Apoe and Gdf15 which are related to the development trajectory of senescent fibroblasts during photoaging.", "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:38195709"], "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:GSE173385"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE173385"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38195709", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-023-51058-4", "sha256": "sha256:a79458d5a5b0da87c11c3f3cf91e46ed9d476a90136efb4cb07a6fb4400dc452", "bytes": 30237, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-023-51058-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10776766", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE173385", "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=GSE173385", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE173385", "version": null, "note": "The datasets analysed during the current study are available in the [GEO] repository. 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[https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173385]. Users can download relevant data for free for research and publish relevant articles.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in the [GEO] repository. [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173385]. 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