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 ( embryonic brain cell extraction using FACS), a method to simultaneously isolate neural, mural, endothelial, and microglial cells to more than 94% purity in ∼4 h. Utilizing EMBRACE we isolate, transcriptionally analyze, 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.

Graphical Abstract

Highlights

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  Isolation of embryonic neural, mural, endothelial, and microglial cells to >94% purity

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  Transcriptome analyses of neural, vascular, and microglial cells from E14.5 brain

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  Generation of inter-cellular communication network with 1,710 unique interactions

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  Established “Brain interactome explorer,” a searchable cell communication database

Abstract

Neuroscience; Developmental Neuroscience; Systems Neuroscience; Techniques in Neuroscience