Glial cells’ 3D ‘maps’ reveal key to brain development

Researchers have completed a detailed three-dimensional epigenomic analysis of four key glial cell populations, ventricular radial glia, outer radial glia, oligodendrocyte precursor cells, and microglia, to map how these support cells orchestrate human neocortex development. Building on prior work demonstrating that chromatin looping regulates neurogenesis, the study identifies cell-type-specific candidate cis-regulatory elements and validates their function using transgenic mouse embryos. This work reveals a link between non-coding genetic variants and neuropsychiatric disorders through cell-type-specific gene regulation, advancing understanding of human-specific gene regulation during corticogenesis. Analysis of chromatin accessibility revealed that outer radial glia (oRG) cell-type-specific candidate cis-regulatory elements (cCREs) exhibit a striking correlation with human accelerated regions (HARs); oRG cCREs are enriched for human accelerated regions compared with other cCREs and a subset of human accelerated regions show activity differences from their chimpanzee orthologues that interact with genes involved in neuronal development. Researchers isolated these distinct glial cell types using fluorescence-activated cell sorting…