Science：马坚/段治军等揭示阿尔茨海默病中的3D基因组重塑

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.