Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain.

Single-cell APA profiling in 2 million human brain cells reveals cell-type-specific genetic regulation linked to neurodegenerative diseases, including Alzheimer’s and Parkinson’s.

• Why it matters: Understanding how APA varies across brain cell types and its genetic control is crucial for uncovering mechanisms underlying neurodegenerative diseases and brain function, which remain largely unexplored.
• What they did: The study mapped APA at single-cell resolution in postmortem brains, integrated APA variation with whole-genome sequencing, and identified 3'aQTLs for over 4,200 genes, revealing their distinct role from expression QTLs.
• The result: Findings show APA influences disease-associated loci, such as SNCA in Parkinson’s, and affects mRNA localization, providing a detailed, cell-type-specific framework for investigating gene regulation and disease heritability.