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

Marlijn Poel, Thomas Ulas, Mark R. Mizee, Cheng-Chih Hsiao, Suzanne S. M. Miedema, Adelia, Karianne G. Schuurman, Boy Helder, Sander W. Tas, Joachim L. Schultze, Jörg Hamann () and Inge Huitinga ()
Additional contact information
Marlijn Poel: Netherlands Institute for Neuroscience
Thomas Ulas: University of Bonn
Mark R. Mizee: Netherlands Institute for Neuroscience
Cheng-Chih Hsiao: Amsterdam University Medical Centers, University of Amsterdam
Suzanne S. M. Miedema: Netherlands Institute for Neuroscience
Adelia: Netherlands Institute for Neuroscience
Karianne G. Schuurman: Netherlands Institute for Neuroscience
Boy Helder: Amsterdam University Medical Centers, University of Amsterdam
Sander W. Tas: Amsterdam University Medical Centers, University of Amsterdam
Joachim L. Schultze: University of Bonn
Jörg Hamann: Netherlands Institute for Neuroscience
Inge Huitinga: Netherlands Institute for Neuroscience

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08976-7

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