人类胶质母细胞瘤脑室下区的单核及空间图谱

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

作者信息

Licón-Muñoz Yamhilette, Avalos Vanessa, Subramanian Suganya, Granger Bryan, Martinez Frank, García-Montaño Leopoldo A, Varela Samantha, Moore Drew, Perkins Eddie, Kogan Michael, Berto Stefano, Chohan Muhammad O, Bowers Christian A, Piccirillo Sara G M

机构信息

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.

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.

出版信息

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

DOI:10.1016/j.celrep.2024.115149

PMID:39752252

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.

摘要

脑室下区（SVZ）是哺乳动物脑中特征最为明确的神经发生区域。我们之前表明，在65%的胶质母细胞瘤（GBM）患者中，SVZ是癌症干细胞样细胞的储存库，这些细胞导致治疗抗性和复发的出现。在此，我们构建了基于单核RNA测序的15例患者肿瘤块和SVZ以及两个组织学正常的SVZ样本作为对照的微环境图谱。我们在SVZ的肿瘤细胞中鉴定出以ZEB1为中心的间充质特征。此外，SVZ微环境的特征是具有肿瘤支持性的小胶质细胞，它们在空间上与肿瘤细胞共存并建立相互作用。最后，差异基因表达分析、配体-受体和传入/传出相互作用的预测以及功能测定表明，白细胞介素（IL）-1β/IL-1RAcP和Wnt-5a/Frizzled-3通路是SVZ中的潜在治疗靶点。我们的数据为GBM患者中SVZ的生物学特性提供了见解，并确定了该微环境的潜在靶点。