Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma
Summary: The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrenc...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015006 |
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| author | Yamhilette Licón-Muñoz Vanessa Avalos Suganya Subramanian Bryan Granger Frank Martinez Leopoldo A. García-Montaño Samantha Varela Drew Moore Eddie Perkins Michael Kogan Stefano Berto Muhammad O. Chohan Christian A. Bowers Sara G.M. Piccirillo |
| author_facet | Yamhilette Licón-Muñoz Vanessa Avalos Suganya Subramanian Bryan Granger Frank Martinez Leopoldo A. García-Montaño Samantha Varela Drew Moore Eddie Perkins Michael Kogan Stefano Berto Muhammad O. Chohan Christian A. Bowers Sara G.M. Piccirillo |
| author_sort | Yamhilette Licón-Muñoz |
| collection | DOAJ |
| description | Summary: The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls. We identify a ZEB1-centered mesenchymal signature in the tumor cells of the SVZ. Moreover, the SVZ microenvironment is characterized by tumor-supportive microglia, which spatially coexist and establish crosstalks with tumor cells. Last, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays reveal that the interleukin (IL)-1β/IL-1RAcP and Wnt-5a/Frizzled-3 pathways represent potential therapeutic targets in the SVZ. Our data provide insights into the biology of the SVZ in patients with GBM and identify potential targets of this microenvironment. |
| format | Article |
| id | doaj-art-45f20f380bac43cfbe3b0ea40238e277 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-45f20f380bac43cfbe3b0ea40238e2772025-08-20T02:26:14ZengElsevierCell Reports2211-12472025-01-0144111514910.1016/j.celrep.2024.115149Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastomaYamhilette Licón-Muñoz0Vanessa Avalos1Suganya Subramanian2Bryan Granger3Frank Martinez4Leopoldo A. García-Montaño5Samantha Varela6Drew Moore7Eddie Perkins8Michael Kogan9Stefano Berto10Muhammad O. Chohan11Christian A. Bowers12Sara G.M. Piccirillo13The Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USAThe Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USABioinformatics Core, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Neurogenomics Laboratory, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USABioinformatics Core, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Neurogenomics Laboratory, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USAThe Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USAThe Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USAUniversity of New Mexico School of Medicine, Albuquerque, NM 87131, USABioinformatics Core, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Neurogenomics Laboratory, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Neurosurgery, University of New Mexico Hospital, Albuquerque, NM 87131, USABioinformatics Core, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Neurogenomics Laboratory, Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Neurosurgery, University of New Mexico Hospital, Albuquerque, NM 87131, USAThe Brain Tumor Translational Laboratory, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA; Corresponding authorSummary: The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and the emergence of recurrence. Here, we build a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass and the SVZ of 15 patients and two histologically normal SVZ samples as controls. We identify a ZEB1-centered mesenchymal signature in the tumor cells of the SVZ. Moreover, the SVZ microenvironment is characterized by tumor-supportive microglia, which spatially coexist and establish crosstalks with tumor cells. Last, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays reveal that the interleukin (IL)-1β/IL-1RAcP and Wnt-5a/Frizzled-3 pathways represent potential therapeutic targets in the SVZ. Our data provide insights into the biology of the SVZ in patients with GBM and identify potential targets of this microenvironment.http://www.sciencedirect.com/science/article/pii/S2211124724015006CP: Cancer |
| spellingShingle | Yamhilette Licón-Muñoz Vanessa Avalos Suganya Subramanian Bryan Granger Frank Martinez Leopoldo A. García-Montaño Samantha Varela Drew Moore Eddie Perkins Michael Kogan Stefano Berto Muhammad O. Chohan Christian A. Bowers Sara G.M. Piccirillo Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma Cell Reports CP: Cancer |
| title | Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma |
| title_full | Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma |
| title_fullStr | Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma |
| title_full_unstemmed | Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma |
| title_short | Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma |
| title_sort | single nucleus and spatial landscape of the sub ventricular zone in human glioblastoma |
| topic | CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015006 |
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