Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors

Abstract

Central nervous system (CNS) malignancies include primary tumors, such as gliomas, and brain metastases (BrMs) originating from diverse extracranial cancers. The blood-brain barrier (BBB) is a key structural component of both primary and metastatic brain cancers. Here, we comprehensively analyzed the two major BBB cell types, endothelial and mural cells, across non-tumor brain tissue, isocitrate dehydrogenase (IDH) mutant (IDH mut) low-grade gliomas, IDH wild-type (IDH WT) high-grade glioblastomas (GBMs), and BrMs from various primary tumors. Bulk and single-cell RNA sequencing, integrated with spatial analyses, revealed that GBMs, but not low-grade gliomas, exhibit significant alterations in the tumor vasculature, including the emergence of diverse pathological vascular cell subtypes. However, these alterations are less pronounced in GBMs than in BrMs. Notably, the BrM vasculature shows higher permeability and more extensive interactions with distinct immune cell populations. This vascular atlas presents a resource toward understanding of tumor-specific vascular features in the brain, providing a foundation for developing vascular- and immune-targeting therapies.

Keywords: IDH WT glioblastoma; IDH mut glioma; RNA sequencing; brain metastasis; endothelial cells; mural cells; vasculature.