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Science:马坚/段治军等揭示阿尔茨海默病中的3D基因组重塑

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TL;DR - A Science study maps single-cell 3D genome and gene-expression changes in Alzheimer’s disease, linking altered chromatin folding to cell-type-specific transcriptional dysfunction. Its Hicformer model shows that 3D genome features improve predictions beyond DNA sequence alone.

  • GAGE-seq jointly measured gene expression and chromatin interactions in postmortem brain cells from Alzheimer’s patients and matched controls.
  • Alzheimer’s cells showed fewer short-range and more long-range genomic contacts, alongside weakened separation between active and inactive compartments.
  • Altered regulatory interactions were associated with microglial aging programs, sex-dependent X-linked gene dysregulation, and disrupted tissue microenvironments.
  • Integrating single-cell multiomics, chromatin accessibility, and spatial transcriptomics produced a multiscale framework for prioritizing disease-related regulatory elements.

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Science:马坚/段治军等揭示阿尔茨海默病中的3D基因组重塑

WeChat: 生物世界 2026-08-11 doi:10.1126/science.adz1652
Public signals OpenAlex citations 0 · Semantic Scholar citations 0 · Semantic Scholar influential citations 0
Providers: Hugging Face · N/A OpenAlex · Citations 0 Publisher · N/A Semantic Scholar · Citations 0 · Influential citations 0 X · N/A Fetched 2026-09-12 14:28:11.544030 UTC

TL;DR - A Science study maps single-cell 3D genome and gene-expression changes in Alzheimer’s disease, linking altered chromatin folding to cell-type-specific transcriptional dysfunction. Its Hicformer model shows that 3D genome features improve predictions beyond DNA sequence alone.

  • GAGE-seq jointly measured gene expression and chromatin interactions in postmortem brain cells from Alzheimer’s patients and matched controls.
  • Alzheimer’s cells showed fewer short-range and more long-range genomic contacts, alongside weakened separation between active and inactive compartments.
  • Altered regulatory interactions were associated with microglial aging programs, sex-dependent X-linked gene dysregulation, and disrupted tissue microenvironments.
  • Integrating single-cell multiomics, chromatin accessibility, and spatial transcriptomics produced a multiscale framework for prioritizing disease-related regulatory elements.
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