A Multi-Regional Single-nucleus Atlas of the Huntington’s Disease Brain

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of the CAG trinucleotide repeat sequence in the HTT gene. Research on HD, a rare condition, relies heavily on donations of post-mortem brain tissue, which are extremely valuable yet difficult to obtain. While numerous studies have published single-nucleus RNA sequencing (snRNA-seq) data from the brain tissues of HD patients, such datasets remain scattered across various public repositories. A lack of standardized metadata and analytical workflows has hindered the integration and reutilization of these resources. To address this challenge, we constructed a curated, multi-brain-region, single-nucleus atlas of controls/HD patients by integrating 104 tissue samples from 39 HD patients and 34 controls, spanning six brain regions: the striatum (caudate and putamen), frontal cortex, cingulate cortex, nucleus accumbens, hippocampus, and cerebellum. This atlas comprises 330,892 cells that have been subjected to standardized quality control, batch effect correction and cell type annotation. Here, we present the first large-scale, multi-region single-nucleus reference atlas for HD, providing a comprehensive resource for the research community. It will serve as a critical data foundation for deepening the investigation of cell-type-specific molecular mechanisms underlying HD, facilitating cross-brain-region experimental validation, and enable the identification of novel therapeutic targets.