Spatial dynamics of brain development and neuroinflammation [Spatial Transcriptomics]
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. Overall design: Samples consist of mouse brain tissue sections collected across normal postnatal development (P0, P2, P5, P7, P10, P21) as well as from a lysolecithin (LPC)-induced demyelination model at multiple recovery stages (5, 10, 21 days post-lesion). Each sample was processed for spatial multi-omic profiling using DBiT-seq. Biological replicates are included for each developmental stage and lesion condition. Experimental variables under investigation include developmental timepoint, brain region, and lesion status (lesion core, distal white matter, and control). These samples enable comparative analyses of spatiotemporal dynamics in brain development and demyelination.