Samples & cell type composition in sc/snRNA-seq.
<div><p>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...
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2025
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| _version_ | 1849927642836369408 |
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| author | Jingxin Zeng (18773484) |
| author2 | Ling Lin (57361) Yangyang Ma (6329852) Wenzhe Huang (446343) Quan Luo (1423180) Ju Wen (14784239) |
| author2_role | author author author author author |
| author_facet | Jingxin Zeng (18773484) Ling Lin (57361) Yangyang Ma (6329852) Wenzhe Huang (446343) Quan Luo (1423180) Ju Wen (14784239) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jingxin Zeng (18773484) Ling Lin (57361) Yangyang Ma (6329852) Wenzhe Huang (446343) Quan Luo (1423180) Ju Wen (14784239) |
| dc.date.none.fl_str_mv | 2025-11-24T18:27:47Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pone.0336502.s008 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Samples_cell_type_composition_in_sc_snRNA-seq_/30696990 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Cell Biology Genetics Neuroscience Biotechnology Immunology Developmental Biology Cancer Hematology Virology Biological Sciences not elsewhere classified Information Systems not elsewhere classified limited treatment efficacy associated tumor cells adhesion genes (< nucleus rna sequencing metastatic tumor subpopulation 26 melanoma samples study identifies mbmatcs mbm ecosystems showed div >< p melanoma brain metastasis metastatic pathways bulk rna brain metastasis melanoma patients validation cohorts upregulated neural treg enrichment remains lethal potential activity nrg3 </ ncam1 </ mela3 ). lag3 </ high risk havcr2 </ early stratification clinical relevance cellular origins cellular origin brain tropism >), suggesting 1 </ |
| dc.title.none.fl_str_mv | Samples & cell type composition in sc/snRNA-seq. |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | <div><p>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 (<i>NRG3</i>, <i>NCAM1</i>), suggesting a cellular origin for brain tropism. MBM ecosystems showed T cell exhaustion (elevated <i>PD-1</i>, <i>HAVCR2</i>, <i>LAG3</i>) 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.</p></div> |
| eu_rights_str_mv | openAccess |
| id | Manara_ba5493a199dea0448bb998ef30dbafcb |
| identifier_str_mv | 10.1371/journal.pone.0336502.s008 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30696990 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Samples & cell type composition in sc/snRNA-seq.Jingxin Zeng (18773484)Ling Lin (57361)Yangyang Ma (6329852)Wenzhe Huang (446343)Quan Luo (1423180)Ju Wen (14784239)Cell BiologyGeneticsNeuroscienceBiotechnologyImmunologyDevelopmental BiologyCancerHematologyVirologyBiological Sciences not elsewhere classifiedInformation Systems not elsewhere classifiedlimited treatment efficacyassociated tumor cellsadhesion genes (<nucleus rna sequencingmetastatic tumor subpopulation26 melanoma samplesstudy identifies mbmatcsmbm ecosystems showeddiv >< pmelanoma brain metastasismetastatic pathwaysbulk rnabrain metastasismelanoma patientsvalidation cohortsupregulated neuraltreg enrichmentremains lethalpotential activitynrg3 </ncam1 </mela3 ).lag3 </high riskhavcr2 </early stratificationclinical relevancecellular originscellular originbrain tropism>), suggesting1 </<div><p>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 (<i>NRG3</i>, <i>NCAM1</i>), suggesting a cellular origin for brain tropism. MBM ecosystems showed T cell exhaustion (elevated <i>PD-1</i>, <i>HAVCR2</i>, <i>LAG3</i>) 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.</p></div>2025-11-24T18:27:47ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.1371/journal.pone.0336502.s008https://figshare.com/articles/dataset/Samples_cell_type_composition_in_sc_snRNA-seq_/30696990CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306969902025-11-24T18:27:47Z |
| spellingShingle | Samples & cell type composition in sc/snRNA-seq. Jingxin Zeng (18773484) Cell Biology Genetics Neuroscience Biotechnology Immunology Developmental Biology Cancer Hematology Virology Biological Sciences not elsewhere classified Information Systems not elsewhere classified limited treatment efficacy associated tumor cells adhesion genes (< nucleus rna sequencing metastatic tumor subpopulation 26 melanoma samples study identifies mbmatcs mbm ecosystems showed div >< p melanoma brain metastasis metastatic pathways bulk rna brain metastasis melanoma patients validation cohorts upregulated neural treg enrichment remains lethal potential activity nrg3 </ ncam1 </ mela3 ). lag3 </ high risk havcr2 </ early stratification clinical relevance cellular origins cellular origin brain tropism >), suggesting 1 </ |
| status_str | publishedVersion |
| title | Samples & cell type composition in sc/snRNA-seq. |
| title_full | Samples & cell type composition in sc/snRNA-seq. |
| title_fullStr | Samples & cell type composition in sc/snRNA-seq. |
| title_full_unstemmed | Samples & cell type composition in sc/snRNA-seq. |
| title_short | Samples & cell type composition in sc/snRNA-seq. |
| title_sort | Samples & cell type composition in sc/snRNA-seq. |
| topic | Cell Biology Genetics Neuroscience Biotechnology Immunology Developmental Biology Cancer Hematology Virology Biological Sciences not elsewhere classified Information Systems not elsewhere classified limited treatment efficacy associated tumor cells adhesion genes (< nucleus rna sequencing metastatic tumor subpopulation 26 melanoma samples study identifies mbmatcs mbm ecosystems showed div >< p melanoma brain metastasis metastatic pathways bulk rna brain metastasis melanoma patients validation cohorts upregulated neural treg enrichment remains lethal potential activity nrg3 </ ncam1 </ mela3 ). lag3 </ high risk havcr2 </ early stratification clinical relevance cellular origins cellular origin brain tropism >), suggesting 1 </ |