Single-cell genomics and regulatory networks for 388 human brains.
Science
; 384(6698): eadi5199, 2024 May 24.
Article
in En
| MEDLINE
| ID: mdl-38781369
ABSTRACT
Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Gene Regulatory Networks
/
Single-Cell Analysis
/
Mental Disorders
Limits:
Humans
Language:
En
Journal:
Science
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos