Comprehensive single-cell atlas of the developing mouse brain

The project aims to generate a comprehensive, spatially- and temporally-resolved, cellular-resolution atlas of the whole developing mouse brain, sampled at high resolution through the entire period of embryonic and postnatal brain development (from E8.0 to P28). This will involve three complementary approaches for multi-omic single-cell profiles: 10x Genomics single-cell RNA-seq (scRNA-seq), 10x Genomics Multiome (simultaneous single-nucleus RNA-seq and ATAC-seq), and Smart-seq3 (for full-length deep RNA-sequencing). In parallel, the spatially resolved transcriptomic method MERFISH will be used across the same timeline to identify spatial distribution of cell types and dynamic changes in cell states. Computational methods will be applied to predict developmental lineage relationships, which will be experimentally validated through barcode-based in vivo lineage tracing and functional testing of candidate molecular effectors using multiplexed in utero CRISPR screening (Perturb-seq). Finally, the project will pilot integration of developmental datasets across species, mapping single-cell omics datasets from developing human and non-human primate brains onto the mouse atlas to create a computational alignment of developmental time.