Spatial dynamics of brain development and neuroinflammation [ADT_data]
The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we deployed spatial tri-omic sequencing including spatial ARP-seq (spatial ATAC–RNA–Protein-seq) and spatial CTRP-seq (spatial CUT&Tag–RNA–Protein-seq), alongside multiplexed immunofluorescence imaging (CODEX), to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21 and compared to the corresponding regions in the human developing brain. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for a subset of layer-defining transcription factors. In the corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions, and a role for layer-specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, were found to be transiently activated not only at the core of the LPC lesion but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, providing a valuable data resource to investigate 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.