{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:20:36Z","timestamp":1791397236119,"version":"4.3.3"},"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Understanding the specific type of brain malignancy, source of brain metastasis, and underlying transformation mechanisms can help provide better treatment and less harm to patients. The tumor microenvironment plays a fundamental role in cancer progression and affects both primary and metastatic cancers. The use of single-cell RNA sequencing to gain insights into the heterogeneity profiles in the microenvironment of brain malignancies is useful for guiding treatment decisions. To comprehensively investigate the heterogeneity in gliomas and brain metastasis originating from different sources (lung and breast), we integrated data from three groups of single-cell RNA-sequencing datasets obtained from GEO. We gathered and processed single-cell RNA sequencing data from 90,168 cells obtained from 17 patients. We then employed the R package Seurat for dataset integration. Next, we clustered the data within the UMAP space and acquired differentially expressed genes for cell categorization. Our results underscore the significance of macrophages as abundant and pivotal constituents of gliomas. In contrast, lung-to-brain metastases exhibit elevated numbers of AT2, cytotoxic CD4+ T, and exhausted CD8+ T cells. Conversely, breast-to-brain metastases are characterized by an abundance of epithelial and myCAF cells. Our study not only illuminates the variation in the TME between brain metastasis with different origins but also opens the door to utilizing established markers for these cell types to differentiate primary brain metastatic cancers.<\/jats:p>","DOI":"10.1371\/journal.pone.0306220","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T17:41:49Z","timestamp":1722015709000},"page":"e0306220","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comprehensive integrated single-cell RNA sequencing analysis of brain metastasis and glioma microenvironment: Contrasting heterogeneity landscapes"],"prefix":"10.1371","volume":"19","author":[{"given":"Seyedeh Fatemeh","family":"Sajjadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7337-4404","authenticated-orcid":true,"given":"Najmeh","family":"Salehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5900-8697","authenticated-orcid":true,"given":"Mehdi","family":"Sadeghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"pone.0306220.ref001","article-title":"Single-Cell Transcriptomics of Glioblastoma Reveals a Unique Tumor Microenvironment and Potential Immunotherapeutic Target Against Tumor-Associated Macrophage","volume":"11","author":"X Cui","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0306220.ref002","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.molonc.2014.05.009","article-title":"Brain metastasis: New opportunities to tackle therapeutic resistance.","author":"J Seoane","year":"2014","journal-title":"Molecular Oncology"},{"key":"pone.0306220.ref003","article-title":"Single\u2010cell RNA sequencing reveals cellular and molecular reprograming landscape of gliomas and lung cancer brain metastases","volume":"12","author":"H Sun","year":"2022","journal-title":"Clin Transl Med"},{"key":"pone.0306220.ref004","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-022-05680-3","article-title":"Single-cell spatial immune landscapes of primary and metastatic brain tumours","volume":"614","author":"E Karimi","year":"2023","journal-title":"Nature"},{"key":"pone.0306220.ref005","article-title":"Reactive astrocytes in brain metastasis","author":"D Wasilewski","year":"2017","journal-title":"Frontiers in Oncology"},{"key":"pone.0306220.ref006","article-title":"Single-Cell Profiling Comparisons of Tumor Microenvironment between Primary Advanced Lung Adenocarcinomas and Brain Metastases and Machine Learning Algorithms in Predicting Immunotherapeutic Responses","volume":"13","author":"Y Wu","year":"2023","journal-title":"Biomolecules"},{"key":"pone.0306220.ref007","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10555-016-9638-9","article-title":"Advances in decoding breast cancer brain metastasis","volume":"35","author":"C Zhang","year":"2016","journal-title":"Cancer Metastasis Rev"},{"key":"pone.0306220.ref008","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cell.2021.12.043","article-title":"Cellular architecture of human brain metastases","volume":"185","author":"H Gonzalez","year":"2022","journal-title":"Cell"},{"key":"pone.0306220.ref009","first-page":"1","article-title":"Functional heterogeneity of CD4+ tumor-infiltrating lymphocytes with a resident memory phenotype in NSCLC","volume":"9","author":"AE Oja","year":"2018","journal-title":"Front Immunol"},{"key":"pone.0306220.ref010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/cancers13040596","article-title":"CD4+ T cells: Multitasking cells in the duty of cancer immunotherapy","volume":"13","author":"JR Richardson","year":"2021","journal-title":"Cancers (Basel)"},{"key":"pone.0306220.ref011","article-title":"Differentiating glioblastomas from solitary brain metastases: An update on the current literature of advanced imaging modalities","author":"AJ Fordham","year":"2021","journal-title":"Cancers. 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