Transcriptional Profiling of Human Microglia Reveals Grey-white Matter Heterogeneity and Multiple Sclerosis-associated Changes

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Mar 15

PMID 30867424

Citations 154

Authors

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

Jorg Hamann

Inge Huitinga

Affiliations

Soon will be listed here.

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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