Single-cell and spatial atlas unveil tumor-specific microenvironment convergence and a prognosis-associated PLXDC1+ myofibroblast population in metastatic bladder cancer
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Le résumé fourni par la source
BACKGROUND: While single-cell technologies have advanced bladder cancer research, the microenvironment of lymph node metastases and its role in progression remain unclear. We aimed to elucidate dynamic tumor-microenvironment interactions across metastatic and primary sites, identify poor-prognosis features, and uncover novel therapeutic targets. METHODS: We profiled matched single-cell and spatial transcriptomic samples from lymph node-metastasized bladder cancer to construct a high-resolution atlas. Bioinformatic analyses were used to inferred ligand-receptor interactions, regulatory networks, and spatial co-localization. Integration with multiple prognostic cohorts revealed key cell subpopulations linked to tumor biology and poor outcomes. RESULTS: Our atlas included 32 samples, 61 cell subtypes, key ligand signals (e.g., TGFB1, OSM, IFNG), 343 transcription factors, 188 co-localization events, over 1,000 spatially validated interactions, and 21 cell niches. Tumor-driven convergence was observed across distinct microenvironments. Notably, a pericyte-like myofibroblast subtype, myoCAF_PLXDC1, was enriched in malignant tissues, associated with poor prognosis, and exhibited enhanced angiogenic but reduced chemotactic activity compared to myoCAF_CCL21. Its phenotype was linked to intracellular regulators (PRRX1 and MXD4) and extracellular signals (IFNG and TGFB1). Spatially, myoCAF_PLXDC1 co-localized with ITGA8+ endothelial cells and enriched in tumor regions. CONCLUSIONS: This study offers a comprehensive resource for lymph node-metastasized bladder cancer and identifies PLXDC1+ fibroblasts co-localized with ITGA8+ ECs as potential components of a tumor-specific vascular niche and therapeutic target.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Single-cell and spatial atlas unveil tumor-specific microenvironment convergence and a prognosis-associated PLXDC1+ myofibroblast population in metastatic bladder cancer
- Date Crossref
- 15/12/2025
- Éditeur
- Springer Science and Business Media LLC
- 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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Second Military Medical University pays non établi dans la noticeUniversité ou école supérieure
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Changhai Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai First People's Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Jiao Tong University pays non établi dans la noticeUniversité ou école supérieure
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Shanghai Sixth People's Hospital pays non établi dans la noticeÉtablissement de santé
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Naval Medical University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Shanghai Jiaotong University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
Second Military Medical University, Changhai Hospital et Shanghai First People's Hospital, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.