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, Suzanne S. M. Miedema, Adelia, Karianne G. Schuurman, Boy Helder, Sander W. Tas, Joachim L. Schultze, J. rg Hamann, Inge Huitinga

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Article number1139
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

Cite this

van der Poel, Marlijn ; Ulas, Thomas ; Mizee, Mark R. ; Hsiao, Cheng-Chih ; Miedema, Suzanne S. M. ; Adelia ; Schuurman, Karianne G. ; Helder, Boy ; Tas, Sander W. ; Schultze, Joachim L. ; Hamann, J. rg ; Huitinga, Inge. / Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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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.",
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van der Poel, M, Ulas, T, Mizee, MR, Hsiao, C-C, Miedema, SSM, Adelia, Schuurman, KG, Helder, B, Tas, SW, Schultze, JL, Hamann, JR & Huitinga, I 2019, 'Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes' Nature Communications, vol. 10, no. 1, 1139. https://doi.org/10.1038/s41467-019-08976-7

Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes. / van der Poel, Marlijn; Ulas, Thomas; Mizee, Mark R.; Hsiao, Cheng-Chih; Miedema, Suzanne S. M.; Adelia; Schuurman, Karianne G.; Helder, Boy; Tas, Sander W.; Schultze, Joachim L.; Hamann, J. rg; Huitinga, Inge.

In: Nature Communications, Vol. 10, No. 1, 1139, 01.12.2019.

Research output: Contribution to journalArticleAcademicpeer-review

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