Scientists unveil largest cellular atlas of the basal ganglia

Researchers from dozens of labs across nine countries released the most detailed multi-species atlas of the basal ganglia, a brain region tied to Parkinson’s, Huntington’s, schizophrenia, bipolar disorder and addiction. The open dataset spans 25.5 million cells and is meant to accelerate research into brain disease and cellular function.

Why it matters: - The basal ganglia is one of the brain’s most disease-relevant regions, with genetic and molecular links to Parkinson’s disease, Huntington’s disease, schizophrenia, bipolar disorder and addiction. - The new atlas gives researchers a shared, cell-by-cell reference for studying how this region works and how disease alters it. - All data is openly available to the scientific community, which could speed follow-on discoveries beyond this project.

What happened: - Researchers across nine countries and more than 50 institutions released the most detailed multi-species cellular atlas of the basal ganglia to date. - The work appears today in a package of 26 studies in the Cell Press family of journals. - The effort profiled 25.5 million cells from humans, rhesus and cynomolgus macaques, and marmosets. - Human data included 21.0 million cells. - Primate data included 3.0 million macaque cells and 1.5 million marmoset cells. - The project used single-cell molecular profiling to measure gene expression in individual cells. - The atlas is the first major working model of a standardized, cross-species brain cell reference atlas. - The atlas is the first major output from the BRAIN Initiative Cell Atlas Network, or BICAN.

The details: - The atlas is intended to serve as a library of brain cell types and datasets across human, macaque, marmoset and mouse. - Researchers used a common reference system to classify and analyze the brain’s cellular complexity for the first time in this effort. - The same molecular classification framework was applied across gene expression, epigenetic regulation, spatial analyses and physiological properties. - The different data types largely agreed with one another, strengthening confidence in the cell-type map. - The project supports BICAN’s larger goal of building a complete atlas of all cell types in the human brain. - The work is funded by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies Initiative and the BRAIN Initiative. - The open framework is meant to establish a shared language for neuroscience research.

Between the lines: - The atlas is significant because brain disease has been harder to map at the cellular level than many other major disease areas. - Team-based science mattered here because the project depended on common standards across many labs and species. - A single, agreed-upon reference could reduce fragmented methods in neuroscience and make results easier to compare across studies. - The early outputs suggest that the basal ganglia may be a useful template for building a broader whole-brain cell atlas.

What the studies found: - One study identified a new brain cell type, STR D2 SMYD2-HTR7, linked to schizophrenia and bipolar disorder. - That study found a rare neuron type expressing the serotonin receptor HTR7 that had not appeared in earlier studies. - The new cell-type map narrows genetic disease signals to a specific population researchers can now investigate. - A UCSF study found key genetic changes in specific basal ganglia cell types that could be involved in autism. - A Broad Institute study found widespread cell-type-specific gene-expression changes associated with aging. - The Broad study also found that a person’s age can be predicted from gene-expression patterns across multiple cell types. - That finding could help form the basis for biological aging clocks built from brain cells.

What’s next: - Researchers will use the atlas as a reference point for future studies of brain development, aging and disease. - The BICAN consortium will continue work toward a complete human brain cell atlas. - The openly shared data is expected to fuel new analyses by scientists worldwide. - The broader goal is to improve understanding and treatment of brain disease by making the cellular organization of the brain easier to study.

The bottom line: - The basal ganglia atlas gives neuroscience a major new common map for one of the brain’s most important disease hubs, and it is built to be reused by the field.