3D Epigenome Maps Glial Lineages to Decode Human Cortical Development

Researchers mapped the 3D epigenome of four glial populations (vRG, oRG, OPCs, microglia) from mid-gestational human cortex, integrating RNA‑seq, ATAC‑seq, WGBS and PLAC‑seq to identify cell‑type–specific cis-regulatory elements and 3D promoter–enhancer interactions. They validated enhancers in mouse embryos, trained machine‑learning models to prioritize disease variants, and found 112 schizophrenia‑risk variants within glial cCREs, including rs4449074 whose risk allele reduces vRG accessibility and forebrain enhancer activity. The study also shows oRG cCREs are enriched for human accelerated regions, suggesting human‑specific regulatory evolution in corticogenesis. This work advances understanding of gene regulation in human cortical development and neuropsychiatric disease risk.