Spatial Perturb-Seq: Single-Cell Functional Genomics within Intact Tissue Architecture

We develop Spatial Perturb-Seq, an in vivo CRISPR technology that interrogates multiple genes within single cells of intact tissues. We apply Spatial Perturb-Seq to screen risk genes for neurodegenerative diseases in the mouse brain, uncovering cell autonomous and cell-cell microenvironmental effects within the spatially intact tissue. Spatial Perturb-Seq functionally screens multiple genes in situ and in vivo, identifying candidate genes underlying dysregulated neuronal intercellular communication pathways in Lrp1 signalling and ephrin-Eph receptor interactions.