Brain Immune Atlas

About

The brain immune atlas provides a resource and visualization tool for assessing various single-cell RNA sequencing datasets that together capture the diversity of the brain immune compartment, as published in Nature Neuroscience (A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment). Using the 10x genomics chromium platform, we analyzed more than 61.000 CD45+ immune cells that were obtained from whole brains or isolated border regions, including the dura mater, subdural meninges and choroid plexus. Datasets were obtained from WT homeostatic mice, conditional Irf8 knockout animals and aged APP/PS1 transgenics.

 
 
 
 
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Summary

While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain.

 

Citation

Hannah Van Hove, Liesbet Martens, Isabelle Scheyltjens, Karen De Vlaminck, Ana Rita Pombo Antunes, Sofie De Prijck, Niels Vandamme, Sebastiaan De Schepper, Gert Van Isterdael, Charlotte L. Scott, Jeroen Aerts, Geert Berx, Guy E. Boeckxstaens, Roosmarijn E. Vandenbroucke, Lars Vereecke, Diederik Moechars, Martin Guilliams, Jo A. Van Ginderachter, Yvan Saeys and Kiavash Movahedi. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nature Neuroscience, 2019.

 

Contact

 

These results were obtained in the teams of Kiavash Movahedi and Yvan Saeys, at the VIB inflammation research center. The online tool was developed by Liesbet Martens. We hope you will find this resource useful and we would be happy to hear about your experiences and suggestions.

 
labFlask Kiavash Movahedi, PhD
Team Leader
Myeloid Cell Immunology Lab
VIB Inflammation Research Center (IRC)
Vrije Universiteit Brussel
Pleinlaan 2, 1050 Brussels, Belgium
Tel: +32-2-6291978
kiavash.movahedi@vub.be
Yvan Saeys, PhD
Team Leader
Data mining and Modeling for Biomedicine Lab
VIB Inflammation Research Center (IRC)
Universiteit Gent
Technologiepark 71, 9052 Zwijnaarde, Belgium
Tel: +32(0)9 331 37 40
bioit@irc.vib-ugent.be
 
 
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