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

Cell Rep. 2025 Jan 28;44(1):115149. doi: 10.1016/j.celrep.2024.115149. Epub 2025 Jan 2.

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.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Interleukin-1beta / metabolism
  • Lateral Ventricles / metabolism
  • Lateral Ventricles / pathology
  • Male
  • Microglia / metabolism
  • Microglia / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Tumor Microenvironment*
  • Wnt-5a Protein / genetics
  • Wnt-5a Protein / metabolism
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Zinc Finger E-box-Binding Homeobox 1
  • Wnt-5a Protein
  • Interleukin-1beta
  • ZEB1 protein, human
  • WNT5A protein, human