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

Jiawei Li1,2, Qin Zhou2, Chunxiang Shi2

  • 1Guangzhou Red Cross Hospital of Jinan University, Jinan University, Guangzhou, China.

Scientific Data
|July 2, 2026
PubMed

Insights

Researchers created a comprehensive single-nucleus reference atlas for Huntington's disease (HD), integrating data from multiple brain regions. This valuable resource aids in understanding HD's molecular mechanisms and identifying therapeutic targets.

Area of Science:

  • Neuroscience
  • Genetics
  • Bioinformatics

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder linked to the HTT gene's CAG repeat expansion.
  • Acquiring post-mortem brain tissue for HD research is challenging, limiting study scope.
  • Existing single-nucleus RNA sequencing (snRNA-seq) data for HD is fragmented across repositories, hindering integration.

Purpose of the Study:

  • To develop a unified, multi-region single-nucleus reference atlas for Huntington's disease research.
  • To overcome limitations posed by scattered datasets and lack of standardized analysis.
  • To provide a foundational resource for investigating HD's cellular and molecular underpinnings.

Main Methods:

  • Integrated 104 post-mortem brain tissue samples from 39 HD patients and 34 controls.
  • Covered six key brain regions: striatum, frontal cortex, cingulate cortex, nucleus accumbens, hippocampus, and cerebellum.
  • Applied standardized quality control, batch correction, and cell type annotation to 330,892 cells.

Main Results:

  • Generated the first large-scale, multi-region single-nucleus reference atlas for Huntington's disease.
  • The atlas comprises 330,892 annotated cells from controls and HD patients.
  • Standardized data processing ensures high-quality, reproducible analysis.

Conclusions:

  • The HD single-nucleus atlas is a comprehensive resource for the research community.
  • Facilitates deeper investigation into cell-type-specific molecular mechanisms of HD.
  • Enables cross-brain-region validation and identification of novel therapeutic targets for Huntington's disease.

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