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Updated: Aug 16, 2026

Isolation of Primary Murine Brain Microvascular Endothelial Cells
Published on: November 14, 2014
Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in
Simone Brioschi1, Julia A Belk2, Steffen E Storck3
1Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, St. Louis, MO 63110, USA; Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
Abstract:
Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During Alzheimer's disease (AD), human perivascular macrophages upregulate cMAF and IGF1 to enhance communication with vascular cells, and this response is abrogated in APOE4 carriers. Lastly, we explore an uncharacterized polymorphism in cMAF, providing evidence that the cMAF program is protective against AD. Targeting cMAF in perivascular macrophages may offer new therapeutic strategies for neurodegenerative and cerebrovascular diseases.
Insights
Cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) regulates brain perivascular macrophages and their communication with blood vessels. Targeting cMAF may offer new therapies for neurodegenerative diseases like Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Brain perivascular macrophages are crucial for brain health, but their regulatory mechanisms and functions are not fully understood.
- Identifying key transcription factors is essential for understanding macrophage function in neurological and cerebrovascular diseases.
Purpose of the Study:
- To identify key transcription factors regulating brain perivascular macrophage function.
- To investigate the role of cMAF in brain perivascular macrophage phenotype, function, and communication with vascular cells.
- To explore the role of cMAF in Alzheimer's disease (AD) pathogenesis and its therapeutic potential.
Main Methods:
- Single-cell multi-omics analysis.
- Conditional gene deletion in vivo experiments.
- Functional assays assessing macrophage-endothelial cell communication and vascular function.
- Analysis of human perivascular macrophages in health and AD, including APOE4 carriers.
Main Results:
- Cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) identified as a key transcription factor for brain perivascular macrophages.
- cMAF deletion disrupts macrophage phenotype and impairs communication with endothelial cells via insulin-like growth factor-1 (IGF1) expression.
- cMAF is conserved in human perivascular macrophages and upregulated in AD, enhancing vascular communication, though this is impaired in APOE4 carriers.
- A cMAF polymorphism suggests a protective role against AD.
Conclusions:
- cMAF is a critical regulator of brain perivascular macrophage function and intercellular communication, impacting vascular health.
- The cMAF-IGF1 pathway in perivascular macrophages plays a significant role in AD pathogenesis.
- Targeting cMAF presents a potential therapeutic strategy for neurodegenerative and cerebrovascular diseases.
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