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A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

Hannah Van Hove, Liesbet Martens (UGent) , Isabelle Scheyltjens, Karen De Vlaminck, Ana Rita Pombo Antunes, Sofie De Prijck (UGent) , Niels Vandamme (UGent) , Sebastiaan De Schepper, Gert Van Isterdael (UGent) , Charlotte Scott (UGent) , et al.
(2019) NATURE NEUROSCIENCE. 22(6). p.1021-1035
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Abstract
While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well 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 capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that 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 both the healthy and diseased brain.
Keywords
CENTRAL-NERVOUS-SYSTEM, GENE-EXPRESSION, DENDRITIC CELLS, MICROGLIA, DISEASE, IRF8, ORIGIN, PRECURSORS, CYTOSCAPE, MONOCYTES

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MLA
Van Hove, Hannah, et al. “A Single-Cell Atlas of Mouse Brain Macrophages Reveals Unique Transcriptional Identities Shaped by Ontogeny and Tissue Environment.” NATURE NEUROSCIENCE, vol. 22, no. 6, 2019, pp. 1021–35, doi:10.1038/s41593-019-0393-4.
APA
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Antunes, A. R. P., De Prijck, S., … Movahedi, K. (2019). A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. NATURE NEUROSCIENCE, 22(6), 1021–1035. https://doi.org/10.1038/s41593-019-0393-4
Chicago author-date
Van Hove, Hannah, Liesbet Martens, Isabelle Scheyltjens, Karen De Vlaminck, Ana Rita Pombo Antunes, Sofie De Prijck, Niels Vandamme, et al. 2019. “A Single-Cell Atlas of Mouse Brain Macrophages Reveals Unique Transcriptional Identities Shaped by Ontogeny and Tissue Environment.” NATURE NEUROSCIENCE 22 (6): 1021–35. https://doi.org/10.1038/s41593-019-0393-4.
Chicago author-date (all authors)
Van Hove, Hannah, Liesbet Martens, Isabelle Scheyltjens, Karen De Vlaminck, Ana Rita Pombo Antunes, Sofie De Prijck, Niels Vandamme, Sebastiaan De Schepper, Gert Van Isterdael, Charlotte Scott, Jeroen Aerts, Geert Berx, Guy E. Boeckxstaene, Roosmarijn Vandenbroucke, Lars Vereecke, Diederik Moechars, Martin Guilliams, Jo A. Van Ginderachter, Yvan Saeys, and Kiavash Movahedi. 2019. “A Single-Cell Atlas of Mouse Brain Macrophages Reveals Unique Transcriptional Identities Shaped by Ontogeny and Tissue Environment.” NATURE NEUROSCIENCE 22 (6): 1021–1035. doi:10.1038/s41593-019-0393-4.
Vancouver
1.
Van Hove H, Martens L, Scheyltjens I, De Vlaminck K, Antunes ARP, De Prijck S, et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. NATURE NEUROSCIENCE. 2019;22(6):1021–35.
IEEE
[1]
H. Van Hove et al., “A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment,” NATURE NEUROSCIENCE, vol. 22, no. 6, pp. 1021–1035, 2019.
@article{8619539,
  abstract     = {{While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well 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 capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that 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 both the healthy and diseased brain.}},
  author       = {{Van Hove, Hannah and Martens, Liesbet and Scheyltjens, Isabelle and De Vlaminck, Karen and Antunes, Ana Rita Pombo and De Prijck, Sofie and Vandamme, Niels and De Schepper, Sebastiaan and Van Isterdael, Gert and Scott, Charlotte and Aerts, Jeroen and Berx, Geert and Boeckxstaene, Guy E. and Vandenbroucke, Roosmarijn and Vereecke, Lars and Moechars, Diederik and Guilliams, Martin and Van Ginderachter, Jo A. and Saeys, Yvan and Movahedi, Kiavash}},
  issn         = {{1097-6256}},
  journal      = {{NATURE NEUROSCIENCE}},
  keywords     = {{CENTRAL-NERVOUS-SYSTEM,GENE-EXPRESSION,DENDRITIC CELLS,MICROGLIA,DISEASE,IRF8,ORIGIN,PRECURSORS,CYTOSCAPE,MONOCYTES}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1021--1035}},
  title        = {{A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment}},
  url          = {{http://dx.doi.org/10.1038/s41593-019-0393-4}},
  volume       = {{22}},
  year         = {{2019}},
}
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