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


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-?B 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.

SUBMITTER: van der Poel M 

PROVIDER: S-EPMC6416318 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

van der Poel Marlijn M   Ulas Thomas T   Mizee Mark R MR   Hsiao Cheng-Chih CC   Miedema Suzanne S M SSM   Adelia   Schuurman Karianne G KG   Helder Boy B   Tas Sander W SW   Schultze Joachim L JL   Hamann Jörg J   Huitinga Inge I  

Nature communications 20190313 1


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 microg  ...[more]

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