{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:33:53Z","timestamp":1783380833294,"version":"3.54.6"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangzhou Basic Research Plan Jointly the City, School","award":["No.2024A03J0483"],"award-info":[{"award-number":["No.2024A03J0483"]}]},{"name":"Talents' plan Foundation of Guangdong Second Provincial General Hospital","award":["No.2024B003"],"award-info":[{"award-number":["No.2024B003"]}]},{"name":"the Science Foundation of Guangdong Second Provincial General Hospital","award":["No.YQ2020-001"],"award-info":[{"award-number":["No.YQ2020-001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Melanoma brain metastasis (MBM) remains lethal with limited treatment efficacy. Meanwhile, the cellular origins and drivers of brain metastasis from melanoma have yet to be defined. Through integrated single-cell\/single-nucleus RNA sequencing of 26 melanoma samples, we identified a pre-brain-metastatic tumor subpopulation (MBMATCs, MBM-associated tumor cells) within a conserved malignant cell trajectory (Mela3). MBMATCs exhibited activated pro-metastatic pathways and upregulated neural\/adhesion genes (\n                    <jats:italic>NRG3<\/jats:italic>\n                    ,\n                    <jats:italic>NCAM1<\/jats:italic>\n                    ), suggesting a cellular origin for brain tropism. MBM ecosystems showed T cell exhaustion (elevated\n                    <jats:italic>PD-1<\/jats:italic>\n                    ,\n                    <jats:italic>HAVCR2<\/jats:italic>\n                    ,\n                    <jats:italic>LAG3<\/jats:italic>\n                    ) and Treg enrichment. An MBM-Index derived from bulk RNA-seq accurately quantifies MBMATCs abundance, independently predicting poor overall survival in both TCGA-SKCM and validation cohorts. Furthermore, we assessed the clinical relevance of the MBM-Index and uncovered five candidate drugs with potential activity against MBMATCs. This study identifies MBMATCs as brain metastasis associated tumor cells and positions the MBM-Index as a biomarker for early stratification of melanoma patients at high risk of brain metastasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0336502","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T18:27:22Z","timestamp":1764008842000},"page":"e0336502","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell transcriptomics profiling reveals cellular origins and molecular drivers underlying melanoma brain metastasis"],"prefix":"10.1371","volume":"20","author":[{"given":"Jingxin","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2470-2589","authenticated-orcid":true,"given":"Ju","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"issue":"3","key":"pone.0336502.ref001","first-page":"229","article-title":"Global 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