The abstract is read at the publisher; the summary is JClub's.
Integrated single-nucleus RNA-seq and ATAC-seq of human hippocampus identifies over 1000 AD-associated cis-regulatory interactions, with EX.CA neurons showing apoptosis-linked chromatin–transcription activation.
- Why it matters: AD vulnerability varies by region and cell type, but the regulatory mechanisms connecting chromatin remodeling to dysfunction are not well defined.
- What they did: The study profiled human hippocampus with single-nucleus RNA-seq and ATAC-seq, linking chromatin accessibility to transcription and inferring regulatory networks across neurons and glia.
- The result: EX.CA neurons show increased accessibility coupled to apoptosis-related gene programs, while EX.DG neurons are comparatively resistant; microglial SPI1/KLF4 and astrocytic STAT3 modules are linked to inflammatory and metabolic transitions, and AD-risk variants are enriched in microglial cis-regulatory elements at BIN1 and APOE, with many regulatory elements human-specific.
The findingWhy it mattersWhat they didThe result
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