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Nat Commun. 2019 Mar 13;10(1):1139. doi: 10.1038/s41467-019-08976-7.

Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes.

Author information

1
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105BA, Amsterdam, The Netherlands.
2
Genomics and Immunoregulation, LIMES Institute, University of Bonn, Carl-Troll-Straße 31, 53115, Bonn, Germany.
3
Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
4
Netherlands Brain Bank, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105BA, Amsterdam, The Netherlands.
5
Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands.
6
PRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Sigmund-Freud-Street 27, 53127, Bonn, Germany.
7
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105BA, Amsterdam, The Netherlands. j.hamann@amc.uva.nl.
8
Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. j.hamann@amc.uva.nl.
9
Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105BA, Amsterdam, The Netherlands. i.huitinga@nin.knaw.nl.

Abstract

Here we report the transcriptional profile of human microglia, isolated from normal-appearing grey matter (GM) and white matter (WM) of multiple sclerosis (MS) and non-neurological control donors, to find possible early changes related to MS pathology. Microglia show a clear region-specific profile, indicated by higher expression of type-I interferon genes in GM and higher expression of NF-κB pathway genes in WM. Transcriptional changes in MS microglia also differ between GM and WM. MS WM microglia show increased lipid metabolism gene expression, which relates to MS pathology since active MS lesion-derived microglial nuclei show similar altered gene expression. Microglia from MS GM show increased expression of genes associated with glycolysis and iron homeostasis, possibly reflecting microglia reacting to iron depositions. Except for ADGRG1/GPR56, expression of homeostatic genes, such as P2RY12 and TMEM119, is unaltered in normal-appearing MS tissue, demonstrating overall preservation of microglia homeostatic functions in the initiation phase of MS.

PMID:
30867424
DOI:
10.1038/s41467-019-08976-7
Free PMC Article

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