Single-Cell Analysis of Brain Arteriovenous Malformations Reveals Pro-Angiogenic Myeloid Programs.

Overview

1. Department of Neurosurgery, Clinical Neuroscience Centre, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland (M.R.G.)
2. Department of Neurosurgery, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany
3. Department of Neuroradiology, Clinical Neuroscience Centre, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland

Abstract

Highlights: What are the main findings? The immune landscape of brain arteriovenous malformations shows a trend towards higher proportions of M1-like macrophages, dendritic cells, monocytes, CD8 T cells and activated T cells compared with control brain tissue. Transcriptional programs related to angiogenesis are enriched in myeloid cell populations including M1-like macrophages, monocytes, and dendritic cells, implicating these immune populations as important contributors to vascular remodeling in brain arteriovenous malformations.

What are the implications of the main findings? The immune microenvironment, and particularly myeloid cell populations, may be associated with pathological vascular remodeling in brain arteriovenous malformations. Targeting immune-mediated angiogenic pathways could represent a potential therapeutic strategy to modulate lesion progression and instability.

Abstract: Background/Objectives: Brain arteriovenous malformations (bAVMs) are complex cerebrovascular lesions that carry a substantial risk of intracranial hemorrhage, yet the biological mechanisms underlying vascular remodeling remain incompletely understood. As increasing evidence suggests that inflammatory processes contribute to vascular remodeling and bAVM progression, this study aimed to characterize the cellular composition of the immune microenvironment in human bAVMs at single-cell resolution and to identify immune cell populations associated with transcriptional programs related to angiogenesis and extracellular matrix remodeling. Methods: Publicly accessible single-cell RNA sequencing data from five human bAVM samples and five control brain specimens were analyzed. After quality control and data integration, immune cell types were annotated based on canonical marker gene expression. To assess biological processes relevant to vascular remodeling, the expression of predefined gene sets associated with angiogenesis and extracellular matrix remodeling, derived from the Molecular Signatures Database (MSigDB), was quantified across cell populations using rank-based gene set scoring (UCell). Differences between bAVM and control samples were evaluated at the sample level using the Wilcoxon rank-sum test. For each immune cell type, mean UCell scores were calculated per biological sample and compared between groups. To account for multiple comparisons across cell types, p-values were adjusted using the Benjamini–Hochberg procedure. Results: After quality control, 46,360 immune cells were analyzed. Compared with control tissue, bAVMs showed numerically higher proportions of lymphoid (activated T cells and CD8 T cells) and myeloid populations (M1-like macrophages, monocytes, and dendritic cells). Angiogenesis-related transcriptional activity was highest in myeloid cells and significantly increased in bAVMs, particularly in M1-like macrophages (UCell score 0.22 vs. 0.13), dendritic cells (0.16 vs. 0.10) and monocytes (0.20 vs. 0.15), whereas proliferating CD8 T cells showed a lower score (0.04 vs. 0.05; adjusted p = 0.040 for all four). Extracellular matrix-related programs showed a similar but weaker and non-significant pattern in myeloid populations (e.g., monocytes, dendritic cells, microglia-like cells; adjusted p = 0.09). Conclusions: Our findings identify myeloid cells, particularly M1-like macrophages, monocytes and dendritic cells, as important immune populations associated with angiogenesis in bAVMs. These findings highlight a potential role of immune-driven vascular remodeling in the pathophysiology of bAVMs.

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Data Availability Statement

The original data analyzed in this study are publicly available at the UCSC Cell Browser repository: https://cells.ucsc.edu/?ds=adult-brain-vasc (accessed on 26 February 2026). All processed data objects and analysis code will be shared upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 6 keywords, 1 funder, 18 references.

Cite

This paper

Beyersdorf, B., Voglis, S., Kulcsar, Z., Regli, L., & Germans, M. R. (2026). Single-Cell Analysis of Brain Arteriovenous Malformations Reveals Pro-Angiogenic Myeloid Programs. Brain sciences, 16(8), 811. https://doi.org/10.3390/brainsci16080811

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