Systematic identification of cell-cell communication networks in the developing brain

Summary Since the generation of cell-type specific knockout models, the importance of inter-cellular communication between neural, vascular and microglial cells during neural development has been increasingly appreciated. However, the extent of communication between these major cell populations remains to be systematically mapped. Here, we describe EMBRACE ( em bryonic bra in c ell e xtraction using FACS), a method to simultaneously isolate neural, mural, endothelial and microglial cells to more than 94% purity in ∼4 hours. Utilising EMBRACE, we isolate, transcriptionally analyse and build a cell-cell communication map of the developing mouse brain. We identify 1,710 unique ligand-receptor interactions between neural, endothelial, mural and microglial cells in silico and experimentally confirm the APOE-LDLR, APOE-LRP1, VTN-KDR and LAMA4-ITGB1 interactions in the E14.5 brain. We provide our data via the searchable “Brain interactome explorer”, available at https://mpi-ie.shinyapps.io/braininteractomeexplorer/. Together, this study provides a comprehensive map that reveals the richness of communication within the developing brain.