Systematic Identification of Cell-Cell Communication Networks in the Developing Brain

Bilal N Sheikh; Olga Bondareva; Sukanya Guhathakurta; Tsz Hong Tsang; Katarzyna Sikora; Nadim Aizarani; Sagar; Herbert Holz; Dominic Grün; Lutz Hein; Asifa Akhtar

doi:10.1016/j.isci.2019.10.026

Systematic Identification of Cell-Cell Communication Networks in the Developing Brain

iScience. 2019 Nov 22:21:273-287. doi: 10.1016/j.isci.2019.10.026. Epub 2019 Oct 17.

Authors

Affiliations

¹ Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, Freiburg 79108, Germany. Electronic address: sheikh@ie-freiburg.mpg.de.
² Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstr. 25, Freiburg 79104, Germany.
³ Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, Freiburg 79108, Germany; Faculty of Biology, Albert Ludwig University of Freiburg, Freiburg 79104, Germany.
⁴ Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, Freiburg 79108, Germany.
⁵ Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, Freiburg 79108, Germany. Electronic address: akhtar@ie-freiburg.mpg.de.

Abstract

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.

Keywords: Developmental Neuroscience; Neuroscience; Systems Neuroscience; Techniques in Neuroscience.