Striatum map reveals six gene-expression zones that blur with age

Researchers at the Broad Institute's Center for Human Brain Variation have identified six zones within the human striatum that are defined by gene expression rather than visible structure. The zones became less distinct with increasing age, and the work also shows how cell-type proportions differ between individuals and shift across adulthood. The studies appear in Cell and Cell Reports Methods as part of the BRAIN Initiative Cell Atlas Network (BICAN).

Why the striatum

The striatum is the largest structure in the basal ganglia, a network that helps regulate movement and behaviour. It is implicated in psychiatric disorders, addiction and neurodegeneration. BICAN, a National Institutes of Health project aiming to build a cellular map of the human brain, chose the basal ganglia as its starting point.

Cell composition varies between people

In the first Cell paper, led by Steven Burger and colleagues in the laboratory of Steve McCarroll, the team applied single-nucleus RNA sequencing to about 4 million cells from the striatum and prefrontal cortex. The tissue came from nearly 200 adult postmortem brains.

The balance of cell types was consistent across different tissues from the same person, but differed considerably between people. The variation was greatest for non-neuronal cells such as astrocytes and microglia. Age-related changes appeared in every region examined. Oligodendrocyte progenitor cells fell in abundance by roughly 40% between ages 30 and 80. Gene expression also shifted with age in all cell types, with especially large changes in projection neurons, which signal to distant brain regions.

Burger said that establishing typical ranges for cell proportions and gene expression gives useful context for disease studies, where distinguishing pathology from normal variation is a persistent difficulty.

Hidden zones and blurring boundaries

The second Cell paper, with Andrew Kraft as first author, used Slide-tags, a spatial method developed by Evan Macosko and Fei Chen that records where individual cells sit in tissue. The team adapted it to cover larger areas and analysed more than 1 million cells across the striatum of 19 postmortem brains.

They found six zones in which projection neurons had distinct gene expression profiles, each apparently linked to particular brain functions. Macosko described this as “hidden histology”: the cells look alike under a microscope, yet the transcriptional differences are strong and consistent between individuals.

Examining more than 130 brains from the first study, the researchers found that the zone boundaries blurred with age, with gene expression differing less from one zone to the next.

A tool for building atlases

A third Broad-led study, in Cell Reports Methods, came from Mehrtash Babadi, Bing-Xing Huo and colleagues. It describes multiVIB, a framework for integrating large single-cell datasets from different molecular modalities. According to the authors, it combines heterogeneous data while limiting incorrect matches and retaining biologically meaningful variation, which should support atlases that can take in new data over time.

Limitations and next steps

All the findings derive from postmortem tissue, and the spatial analysis covered 19 brains, a smaller sample than the cell-composition work. The source does not report links between the zones and specific diseases, so their clinical relevance remains to be tested.

The data and workflows for the variation and zone studies have been shared openly, along with a portal for exploring them. The multiVIB software and tutorials are available on GitHub and Zenodo. Kiku Ichihara, managing director of the centre, said the group will now apply the same methods to the rest of the brain through BICAN.

Source: Key brain area reveals distinct zones whose boundaries blur with age (Medical Xpress, 13 November 2026).

Image: AI-generated illustration.