دورية أكاديمية
أعرض في EDS

Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche.

التفاصيل البيبلوغرافية
العنوان: Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche.
المؤلفون: Liu M; Computational Biology and Bioinformatics Program, Duke University School of Medicine, Durham, NC, 27710, USA.; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA.; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27705, USA., Ji Z; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, 27710, USA., Jain V; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27705, USA., Smith VL; Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA., Hocke E; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27705, USA., Patel AP; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA., McLendon RE; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA.; Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA., Ashley DM; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA., Gregory SG; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA. simon.gregory@duke.edu.; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, 27705, USA. simon.gregory@duke.edu.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA. simon.gregory@duke.edu., López GY; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, 27710, USA. giselle.lopez@duke.edu.; Department of Neurosurgery, Duke University School of Medicine, Durham, NC, 27710, USA. giselle.lopez@duke.edu.; Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA. giselle.lopez@duke.edu.
المصدر: Acta neuropathologica communications [Acta Neuropathol Commun] 2024 Apr 22; Vol. 12 (1), pp. 64. Date of Electronic Publication: 2024 Apr 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2013]-
مواضيع طبية MeSH: Glioblastoma*/genetics , Glioblastoma*/pathology , Glioblastoma*/metabolism , Brain Neoplasms*/genetics , Brain Neoplasms*/pathology , Brain Neoplasms*/metabolism , Tumor Microenvironment*/genetics , Tumor Microenvironment*/immunology , Transcriptome*, Humans
مستخلص: Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into neural progenitor-like (NPC-like), oligodendrocyte-progenitor-like (OPC-like), astrocyte-like (AC-like) and mesenchymal like (MES-like) states, it does not capture the spatial localization of these tumor cell states. Spatial transcriptomics empowers the study of the spatial organization of different cell types and tumor cell states and allows for the selection of regions of interest to investigate region-specific and cell-type-specific pathways. Here, we obtained paired 10x Chromium single-nuclei RNA-sequencing (snRNA-seq) and 10x Visium spatial transcriptomics data from three GBM patients to interrogate the GBM microenvironment. Integration of the snRNA-seq and spatial transcriptomics data reveals patterns of segregation of tumor cell states. For instance, OPC-like tumor and NPC-like tumor significantly segregate in two of the three samples. Our differentially expressed gene and pathway analyses uncovered significant pathways in functionally relevant niches. Specifically, perinecrotic regions were more immunosuppressive than the endogenous GBM microenvironment, and perivascular regions were more pro-inflammatory. Our gradient analysis suggests that OPC-like tumor cells tend to reside in areas closer to the tumor vasculature compared to tumor necrosis, which may reflect increased oxygen requirements for OPC-like cells. In summary, we characterized the localization of cell types and tumor cell states, the gene expression patterns, and pathways in different niches within the GBM microenvironment. Our results provide further evidence of the segregation of tumor cell states and highlight the immunosuppressive nature of the necrotic and perinecrotic niches in GBM.
(© 2024. The Author(s).)
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معلومات مُعتمدة: P50 CA190991 United States CA NCI NIH HHS; KL2 TR002554 United States TR NCATS NIH HHS; 5P50CA190991 United States CA NCI NIH HHS; P30 CA014236 United States CA NCI NIH HHS; 1KL2TR002554 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Glioblastoma; Perinecrotic niche; Perivascular niche; Single-cell sequencing; Spatial transcriptomics; Tumor microenvironment
تواريخ الأحداث: Date Created: 20240422 Date Completed: 20240424 Latest Revision: 20240426
رمز التحديث: 20240426
مُعرف محوري في PubMed: PMC11036705
DOI: 10.1186/s40478-024-01769-0
PMID: 38650010
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-5960
DOI:10.1186/s40478-024-01769-0