A new UCSF study maps more than 1.5 million cells and uncovers specialized cellular “neighborhoods” along arteries, capillaries, and veins — paving the way for precision medicine in cerebrovascular disease.
Despite their involvement in serious neurological conditions such as stroke and amyotrophic lateral sclerosis (ALS), blood vessels remain incompletely understood because researchers have lacked a full picture of all their cell types and organization across the brain.
New research from UC San Francisco now offers the most comprehensive atlas to date of the different cell populations in the brain’s blood vessels. How these cells function is not only affected by the genes they express, but also where they’re located and the other cells in their “neighborhood.”
“Being able to confidently describe the cell composition of the vasculature and where these cells are located lays the foundation for everything else,” said Ethan Winkler, MD, PhD, an assistant professor of Neurological Surgery and the senior author of the study published on July 31 in Cell. “If you don’t know what’s normal, you don’t know how to interpret what’s going awry in disease.”
What’s in a name?
Large-scale neuroscience consortia, like the Brain Initiative Cell Census Network (BICCN), are revealing how the coordination between many different types of neurons enables the brain to perform its wide-ranging functions. But these efforts have largely neglected the brain’s blood vessels.
Here, Winkler and his colleagues integrated data from five previous single-cell sequencing studies, including his lab’s 2022 study focused on the cells in arteriovenous malformations. Their analysis defined 11 cell types based on their gene expression patterns.
They were also able to identify which cells are truly part of the vasculature rather than the meninges, providing a validated reference of the normal composition of the blood vessels. This may seem niche, but saying a cell is from the vasculature when it’s actually from the meninges is like saying someone is from San Francisco when they’re really from Daly City.
As single-cell sequencing technology becomes more widely available, resources like this are critical for the scientific community when designing research and sharing data.
Winkler’s lab then used this new taxonomy of all cell types in blood vessels to map the location of more than 1.5 million cells across the human temporal cortex and hippocampus.
“What we’ve now defined is the very stereotyped patterning that underlies the functional sub-specialization of different segments of the blood vessels in the brain,” Winkler said.
Until now, our understanding of the functional organization of cells in different parts of the blood vessel was incomplete and a “best educated guess,” he added.
While the map offers the most comprehensive atlas of the brain’s vasculature, it only charts the hippocampus and one specific region of the cortex. Other brain regions are structured differently, and it is not yet clear how regional differences in the vasculature may affect neurologic function.
A roadmap for studying disease
For Winkler, who is a vascular neurosurgeon, this study represents more than just an arcane exercise in classifying a cell. The atlas also provides a foundation for understanding and treating diseases that affect his patients.
For example, the cells that make up the transition points along the arteriovenous axis — from arteries and arterioles to venules and veins — may help explain why different segments are selectively vulnerable to different diseases and present new opportunities for more precisely targeted therapies. The atlas could also potentially help develop new molecular biomarkers to aid in the prevention of stroke and other cerebrovascular diseases.
To that end, the researchers overlaid genetic risk factors for various diseases identified in prior genome-wide association studies across specific blood vessel segments. The researchers connected particular vascular cells and vessel segments with genetic risk for stroke, cerebral small vessel disease, ALS, multiple sclerosis, migraine, and others.
In cerebral small vessel disease, a condition that can lead to strokes and dementia in older adults, they showed that the point of vulnerability appears to be the arteriole. In this section of the vessel, the mural cell is a matrix pericyte, and genes that correlate with a higher risk of small vessel disease are also enriched in the matrix pericytes. With a reference point for comparison, scientists can further corroborate these results and identify potential therapeutic strategies to target the abnormal cells.
“The entire gene therapy toolbox could potentially be applied to disease now that we know where and what to target,” Winkler said.
The neighborhood effect
In other neurological diseases, like brain cancer, scientists have learned that abnormal cells do not exist in isolation, and their interaction with neighboring cells shapes the course of disease progression.
Winkler’s team mapped the spatial relationships between blood vessels and neurons. They found that the vascular cells maintained the same distance from neurons but differed in their organization in different brain regions, suggesting regional specialization and possibly co-development with neurons. This establishes vascular cells as part of a dynamic microenvironment that may affect normal functioning and disease states.
The study also systematically defines which subpopulations of immune cells are present in the blood vessels and how they may modulate different pathological states. Knowing the composition of the immune microenvironment helps to better understand the role of inflammation in vascular disease.
Taken together, a detailed catalog of the cell types present in the brain’s blood vessels uncovers opportunities for therapeutic intervention.
“This is setting the stage for precision medicine in stroke to have its moment,” Winkler said.
Reference: Wang et al., Spatial atlas of the human brain vasculature reveals specialized cell ensembles, Cell (2026), https://doi.org/10.1016/j.cell.2026.07.007
This work has been supported by the National Institutes of Neurological Disorders and Stroke (1F31NS147788) (to J.C.W), Shuri and Kay Curci Foundation Award, Marcus Precision Medicine Grant, and Cerebrovascular Section / Congress of Neurological Surgeons Foundation Young Investigators Research Grant (to E.A.W).