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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724015006
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Summary: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.
ISSN:2211-1247