A Community Standard Multispecies Cell Atlas of the Basal Ganglia

Abstract

The NIH BRAIN Initiative Cell Atlas Network (BICAN) aims to generate a standardized, integrated cell atlas of the human, macaque, marmoset, and mouse brain that serves as a foundational community reference for the classification and study of brain cell types. Here we present the first major component of this effort: a cross-species, multimodal atlas of the basal ganglia, a group of subcortical nuclei central to motor control and implicated in a broad range of neurological disorders. Grounded in large-scale single-cell transcriptomic classification and integrated with epigenomic and spatial genomic modalities, this resource is enabled by coordinated cross-species sampling and harmonized analytical frameworks. It provides extensive phenotypic characterization of cell types, incorporates community-informed annotation, and establishes a highly curated, data-driven taxonomy with standardized nomenclature. The atlas is anchored to species-specific anatomical reference frameworks and linked across species through unified structural ontologies, enabling consistent cross-species comparisons. Multiple complementary datasets are mapped to this reference, including multiomic profiles and developmental trajectories aligned to adult cell states. Realization of this resource has required coordinated standards for tissue processing across human and model organisms, harmonization of donor metadata across brain banks, and the development of unified anatomical reference systems. To support these advances, BICAN has established an integrated ecosystem comprising standardized sequencing pipelines, neuroanatomically grounded data infrastructure, scalable visualization and mapping tools, and interoperable metadata standards. Analogous to the standardization achieved in genome science, this ecosystem provides a FAIR (findable, accessible, interoperable, and reusable) framework that enables researchers to map, compare, and interpret diverse datasets against a shared reference and associated knowledge base. The BICAN reference system is now being extended to the whole brain, with principles that are readily generalizable to other organ systems.