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

Marlijn van der Poel; Thomas Ulas; Mark R Mizee; Cheng-Chih Hsiao; S.S.M. Miedema; null Adelia; Karianne G Schuurman; Boy Helder; Sander Tas; Joachim Schultze; Jörg Hamann; Inge Huitinga

doi:10.1038/s41467-019-08976-7

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

Marlijn van der Poel, Thomas Ulas, Mark R Mizee, Cheng-Chih Hsiao, S.S.M. Miedema, Adelia, Karianne G Schuurman, Boy Helder, Sander Tas, Joachim Schultze, Jörg Hamann, Inge Huitinga

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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.

Original language	English
Article number	1139
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08976-7
Publication status	Published - 13 Mar 2019
Externally published	Yes

Funding

The authors acknowledge the Netherlands Brain Bank (https://www.brainbank.nl) for providing the donor material and A. Konstantoulea for performing RT-qPCR experiments. This study was supported by the Dutch MS Research Foundation (grant 13\u2013830 MS), the Thyssen Foundation (2015\u201300387), and the German Research Foundation (FOR 2149).

Funders	Funder number
Dutch MS Research Foundation	13–830 MS
Thyssen Foundation	2015–00387
Deutsche Forschungsgemeinschaft	FOR 2149
Deutsche Forschungsgemeinschaft

Keywords

Microglia
Multiple Sclerosis
Transcriptomics

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Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changesFinal published version, 1.24 MBLicence: CC BY

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van der Poel, M., Ulas, T., Mizee, M. R., Hsiao, C.-C., Miedema, S. S. M., Adelia, Schuurman, K. G., Helder, B., Tas, S., Schultze, J., Hamann, J., & Huitinga, I. (2019). Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes. Nature Communications, 10(1), Article 1139. https://doi.org/10.1038/s41467-019-08976-7

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

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