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However, the detailed molecular profiling of the metastatic bone ecosystem is not fully understood, hindering the development of effective therapies for advanced patients. In this study, we examined the cellular heterogeneity between primary tumours and BM from tissues and peripheral blood by single\u2010cell transcriptomic analysis, which was verified using multiplex immunofluorescence staining and public datasets. Our results demonstrate a senescent microenvironment in BM tissues of NSCLC. BM has a significantly higher infiltration of malignant cells with senescent characteristics relative to primary tumours, accompanied by aggravated metastatic properties. The endothelial\u2010mesenchymal transition involved with SOX18 activation is related to the cellular senescence of vascular endothelial cells from BM. CD4Tstr cells, with pronounced stress and senescence states, are preferentially infiltrated in BM, indicating stress\u2010related dysfunction contributing to the immunocompromised environment during tumour metastasis to bone. Moreover, we identify the SPP1 pathway\u2010induced cellular crosstalk among T cells, vascular ECs and malignant cells in BM, which activates SOX18 and deteriorates patient survival. Our findings highlight the roles of cellular senescence in modulating the microenvironment of BM and implicate anti\u2010senescence therapy for advanced NSCLC patients.<\/jats:p>","DOI":"10.1111\/cpr.13743","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T01:39:41Z","timestamp":1725500381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Single\u2010cell transcriptomic analysis of the senescent microenvironment in bone metastasis"],"prefix":"10.1111","volume":"58","author":[{"given":"Shenglin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Fujian Institute of Orthopaedics, The First Affiliated Hospital of Fujian Medical University  Fuzhou China"},{"name":"Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics School of Medical Technology and Engineering, Fujian Medical University  Fuzhou 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