Molecular mapping of 8 million cells brings cerebral architecture into focus

by University of California, Irvine

edited by Lisa Lock, reviewed by Robert Egan

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University of California, Irvine researchers have mapped approximately 8 million cells in regions deep within the human brain, identifying 60 distinct types and revealing how they form cellular communities. The work offers a foundational reference for investigating brain systems affected by Parkinson's disease, Huntington's disease and other neurological and psychiatric disorders.

The atlas focuses on the basal ganglia, a group of interconnected structures involved in movement, motivation, habits and decision-making. By examining both the molecular characteristics of cells and their locations, scientists are building a more precise picture of how these areas are organized and creating a basis for exploring what changes in disease.

The study, published in Cell, is one of two led by UC Irvine's Center for Neural Circuit Mapping in a coordinated publication package from the BRAIN Initiative Cell Atlas Network. The university's team also contributed to four additional Cell papers on brain cells' molecular features and their similarities across species.

Directing UC Irvine's participation is Xiangmin Xu, chancellor's professor of anatomy and neurobiology in the School of Medicine and director of the Center for Neural Circuit Mapping, which brings together campus expertise in neuroscience, genomics, engineering and computational sciences to foster collaborative research on brain organization, function and neurological disorders.

"Knowing which cells exist in the brain is only part of the story," Xu said. "We also need to know where those cells are located, which other cells surround them and how they're organized within specific brain structures."

Mapping cells within their communities

Single-cell sequencing has transformed scientists' ability to distinguish brain cell types by examining gene activity. The process generally separates cells from their original positions, removing information about their surroundings.

The UC Irvine-led team used spatial transcriptomics, which measures gene activity while retaining information about where cells sit in tissue. Combining two technologies, MERFISH+ and Stereo-seq, researchers analyzed brain samples from four neurotypical donors to connect molecular cell identities with the anatomy of the human basal ganglia.

The study showed that different cell types occupy distinct areas within the basal ganglia. Some supporting cells clustered along the borders between compartments, while certain kinds of neurons that are more abundant in primates were found only within particular compartments.

For Xu, a central advance is the ability to probe cellular communities: the combinations of cells found together in particular locations. These relationships provide insights that a list of cell types alone cannot capture.

UC Irvine researchers led large-scale data generation, computational analysis and the integration of molecular findings with anatomical organization. Bereket Tesfay Berackey, Zhiqun Tan, Ginny Wu and Sujan Das are among the study's major authors. Bogdan Bintu, an assistant professor at UC San Diego, was a key collaborator in technology development, experimental design and data analysis.

A baseline for investigating disease vulnerability

The resulting reference gives scientists a framework for comparing tissue from people with and without brain disorders. Researchers could use it to investigate why particular cell populations are vulnerable to disease while others remain relatively resistant—and whether surrounding cells help explain those differences.

Over time, that work could support more precise experimental models and aid in identifying potential therapeutic targets. The multiscale spatial atlas itself is a foundational research resource; its clinical value depends on the studies that follow.

The tissue pipeline behind the atlas

UC Irvine's second lead study, published in Cell Systems, describes the infrastructure needed for such mapping: a coordinated program for obtaining, preparing and characterizing donated human brain tissue.

With Jillian V. Berry, Bryan M. Tran, P. Adolfo Sequeira and Lorena Valenzuela as primary authors, the paper details workflows connecting donor identification and tissue recovery with the quality standards and anatomical documentation required for advanced molecular research.

The campus's brain procurement program manages brain donation and tissue collection through partnerships with the Orange County Coroner's Office, UC Irvine's Willed Body Program, UCI Health—Orange, CHOC and OneLegacy, a Southern California organ, eye and tissue recovery organization. The study also identifies challenges in recruiting donors who reflect Southern California's population and highlights opportunities to expand outreach and donation pathways.

The two studies demonstrate the value of UC Irvine's involvement in the BRAIN Initiative Cell Atlas Network's effort to generate a comprehensive reference atlas of brain cell types.

"UC Irvine's distinctive contribution is our ability to connect the entire research process, from high-quality human brain tissue procurement and characterization to advanced spatial genomics and construction of detailed human brain reference atlases," Xu said.

Shared standards for broader brain mapping

BICAN's broader publication package brings together hundreds of scientists from 55 institutions across nine countries to produce a common framework for categorizing and comparing basal ganglia cells from different species. These shared classifications help researchers connect findings across laboratories and assess how discoveries in animal models relate to human biology.

The effort also establishes methods and standards intended to guide future mapping of the rest of the brain.

BICAN was launched in 2022. UC Irvine participates through the Center for Multiomic Human Brain Cell Atlas project, alongside the Salk Institute, UC San Diego and Washington University in St. Louis.

Xu compares BICAN's long-term potential to the Human Genome Project, which gave researchers a common reference for studying genes and genetic variation. A brain atlas faces a different challenge: integrating many types of molecular information with the complex arrangement of cells and circuits.

At UC Irvine's Center for Neural Circuit Mapping, the next step is to connect these molecular maps with studies of anatomical connections, cell activity and disease-related changes.

"We are building fundamental reference resources that can serve researchers for many years, enabling discoveries that extend well beyond the original studies," Xu said.

Publication details

Bereket Tesfay Berackey et al., Multiscale spatial atlas of human basal ganglia cell types and communities, Cell (2026). DOI: 10.1016/j.cell.2026.09.027

Jillian V. Berry et al., UC Irvine's BRAIN Initiative Cell Atlas Network (BICAN) Brain Procurement Program for the Center for Multiomic Human Brain Cell Atlas Project, Cell Systems (2026). DOI: 10.1016/j.cels.2026.101778

Journal information: Cell Systems , Cell

Key medical concepts

Basal GangliaSpatial Transcriptomics

Clinical categories

Neurology Provided by University of California, Irvine Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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