Asthma Exacerbations: Integrative Analysis of Mirna Activity in Using Single-cell Transcriptomics
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Le résumé fourni par la source
Abstract Background Asthma exacerbations are caused by dysregulated cellular interactions between airway and immune cell populations. Circulating microRNAs (miRNAs) are potential biomarkers for asthma exacerbations; however, their target airway cells remain poorly defined. Objective To identify the cell types that are regulated by the circulating microRNAs linked to asthma exacerbations and the extent to which the cells are regulated by miRNAs. Methods We integrated a curated panel of exacerbation-associated circulating miRNAs with single-cell RNA sequencing (scRNA-seq) profiles from induced sputum of 16 asthma patients and 8 healthy controls. Experimentally validated miRNA-target interactions were combined with cell-type-specific differential expression. Elastic Net regression and SHAP analysis quantified gene-level regulatory contributions, yielding a composite Regulation Strength metric. Findings were validated against four independent GEO datasets. Results Immune cells, including monocytes, dendritic cells, and macrophages, demonstrated the strongest statistically significant miRNA regulatory signals, in contrast to airway epithelial cells.hsa-miR-222-3p showed opposing regulatory effects in mature versus alveolar macrophages, indicating differentiation-state-dependent activity, while B_Plasma cells showed no detectable regulatory effect from any miRNA tested. Independent GEO validation confirmed higher expression of protective miRNAs (hsa-miR-126-3p, hsa-miR-146b-5p) in healthy individuals, consistent with prior CAMP cohort associations. Conclusion Circulating miRNAs show cell-type-specific regulatory activity, strongest in monocytes, dendritic cells, and macrophages. hsa-miR-222-3p showed opposing regulatory directions between macrophage subtypes, while B_Plasma cells showed no effect, validated across independent GEO cohorts.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Asthma Exacerbations: Integrative Analysis of Mirna Activity in Using Single-cell Transcriptomics
- Date Crossref
- 01/05/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of California San Diego Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Yale University Department of Internal Medicine pays non établi dans la noticeUniversité ou école supérieure
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Yale Cancer Center pays non établi dans la noticeStructure de recherche
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Brigham and Women's Hospital Medicine pays non établi dans la noticeÉtablissement de santé
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Harvard University pays non établi dans la noticeUniversité ou école supérieure
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Boston Children's Hospital Computational Health Informatics pays non établi dans la noticeÉtablissement de santé
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Yale School of Medicine Yale Center for Asthma and Airway Disease pays non établi dans la noticeUniversité ou école supérieure
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channing division of network medicine pays non établi dans la noticeInstitution
Pediatrics — University of California San Diego, Department of Internal Medicine — Yale University et Yale Cancer Center, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.