Spatial dynamics of brain development and neuroinflammation [Epigenomic_data]

Spatially mapping multiple omics layers across time enables dissection of mechanisms underlying brain development, differentiation, arealization, and disease. Here, we deploy spatial tri-omics to chart spatiotemporal remodeling in development and neuroinflammation. We generate a tri-omic atlas of mouse brain from postnatal day P0–P21 and compare corresponding regions in developing human brain. In cortex, a subset of layer-defining transcription factors shows temporally persistent and spatially spreading chromatin accessibility. In corpus callosum, myelin genes exhibit dynamic chromatin priming across subregions, and layer-specific projection neurons appear to coordinate axonogenesis and myelination. In a lysolecithin (LPC) model, we observe molecular programs shared between development and neuroinflammation. Microglia display conserved and distinct inflammatory and resolution programs and are transiently activated both at lesion cores and at distal sites, presumably via neuronal circuitry. These data reveal common and divergent mechanisms and provide a resource for studying brain development, function, and disease.