Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma

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

doi:10.1016/j.celrep.2024.115149

Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma

Cell Rep. 2025 Jan 2;44(1):115149. doi: 10.1016/j.celrep.2024.115149. Online ahead of print.

Affiliations

¹ The 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.
² Bioinformatics 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, USA.
³ University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
⁴ Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS 39216, USA.
⁵ Department of Neurosurgery, University of New Mexico Hospital, Albuquerque, NM 87131, USA.
⁶ The 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. Electronic address: spiccirillo@salud.unm.edu.

PMID: 39752252
DOI: 10.1016/j.celrep.2024.115149

Abstract

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.

Keywords: CP: Cancer; brain tumors; cancer stem-like cells; glioblastoma; sub-ventricular zone; tumor microenvironment.