3D epigenome of glial cell types in developing human cortex

Key Points:

• Researchers isolated and fixed cells from the developing human cortex (GW15-GW24) for multi-omic analyses including FACS, RNA-seq, ATAC-seq, WGBS, and PLAC-seq, ensuring high-quality data with rigorous protocols and quality controls.
• Cell-type-specific chromatin accessibility, gene expression, DNA methylation, and chromatin interactions were characterized, enabling identification of candidate cis-regulatory elements (cCREs) and transcription factor motif enrichments linked to neurodevelopmental cell types.
• Functional validation included mouse enhancer transgenic assays and CRISPR interference targeting human accelerated regions (HARs), demonstrating regulatory activity and effects on neural progenitor proliferation.
• Advanced computational analyses such as single-cell RNA-seq integration, LDSC regression for neuropsychiatric disorder heritability, and machine learning models (GKM-SVM) were employed to predict variant effects and regulatory element functions.
• Ethical compliance was ensured for human prenatal tissue use and animal experiments, with approvals from institutional review boards and animal welfare committees.