Cell-type-specific transposon demethylation and TAD remodeling in aging mouse brain - PubMed
a day ago
- #single-cell analysis
- #epigenetics
- #brain aging
- Aging is a major risk factor for neurodegenerative diseases, with unclear epigenetic mechanisms.
- A comprehensive single-nucleus cell atlas of brain aging was created, including 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei.
- Integration with transcriptomic and chromatin accessibility data identified 36 major cell types.
- Transposable element (TE) methylation distinguished age groups, showing cell-type-specific genome-wide demethylation.
- Chromatin conformation analysis revealed age-related increases in topologically associated domain (TAD) boundary strength with enhanced accessibility at CTCF binding sites.
- Spatial transcriptomics across 895,296 cells showed regional heterogeneity during aging within identical cell types.
- Deep-learning models were developed to predict age-related gene expression changes using multi-modal epigenetic features.
- Age-related comparisons used a 2-month baseline reflecting late-adolescent/early-young adult stage.