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Updated: Sep 3, 2025
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
New Insights into Cerebral Vessel Disease Landscapes at Single-Cell Resolution: Pathogenetic and Therapeutic
Megi Meneri1,2, Sara Bonato3, Delia Gagliardi1,2
1Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy.
Insights
Single-cell RNA sequencing reveals cellular details of cerebrovascular diseases. This technology helps identify new therapeutic targets for conditions like stroke and vascular dementia by analyzing immune responses in blood and vessel cells.
Area of Science:
- Biomedical Science
- Genomics
- Cardiovascular Research
Background:
- Cerebrovascular diseases are a major global health concern, causing significant death and disability.
- Current therapeutic target development is hindered by incomplete understanding of the cellular and molecular basis of these diseases.
Purpose of the Study:
- To explore the utility of omics technology, specifically RNA sequencing, for studying cerebrovascular diseases.
- To investigate cellular heterogeneity and molecular mechanisms in diseased cerebral vessels at single-cell resolution.
Main Methods:
- Utilized single-cell RNA sequencing to analyze high-dimensional profiles of individual blood and vessel cells.
- Applied RNA sequencing in animal models to track cellular alterations in atherosclerotic plaques.
- Employed single-cell transcriptomics in humans to map molecular and cellular levels of cerebral artery plaques.
Main Results:
- Dissected the heterogeneity of diseased cerebral vessels, including atherosclerotic plaques, microenvironment, cell trajectory, and immune responses.
- Tracked individual cells (immune, endothelial, smooth muscle) in animal models and their changes during plaque development.
- Mapped human cerebral artery plaques at molecular and cellular levels, identifying specific immune cells like lymphocytes and macrophages.
Conclusions:
- Single-cell RNA sequencing provides unprecedented resolution for studying cerebrovascular disease mechanisms.
- This approach aids in identifying novel immune targets for therapeutic intervention in stroke and vascular dementia.
- Multi-omics single-cell technologies promise to generate precise cellular signatures for tailored cerebrovascular disease treatments.
Abstract:
Cerebrovascular diseases are a leading cause of death and disability globally. The development of new therapeutic targets for cerebrovascular diseases (e.g., ischemic, and hemorrhagic stroke, vascular dementia) is limited by a lack of knowledge of the cellular and molecular biology of health and disease conditions and the factors that cause injury to cerebrovascular structures. Here, we describe the role of advances in omics technology, particularly RNA sequencing, in studying high-dimensional, multifaceted profiles of thousands of individual blood and vessel cells at single-cell resolution. This analysis enables the dissection of the heterogeneity of diseased cerebral vessels and their atherosclerotic plaques, including the microenvironment, cell evolutionary trajectory, and immune response pathway. In animal models, RNA sequencing permits the tracking of individual cells (including immunological, endothelial, and vascular smooth muscle cells) that compose atherosclerotic plaques and their alteration under experimental settings such as phenotypic transition. We describe how single-cell RNA transcriptomics in humans allows mapping to the molecular and cellular levels of atherosclerotic plaques in cerebral arteries, tracking individual lymphocytes and macrophages, and how these data can aid in identifying novel immune mechanisms that could be exploited as therapeutic targets for cerebrovascular diseases. Single-cell multi-omics approaches will likely provide the unprecedented resolution and depth of data needed to generate clinically relevant cellular and molecular signatures for the precise treatment of cerebrovascular diseases.
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