TY - JOUR
T1 - Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes
AU - van der Poel, Marlijn
AU - Ulas, Thomas
AU - Mizee, Mark R.
AU - Hsiao, Cheng-Chih
AU - Miedema, Suzanne S. M.
AU - Adelia, null
AU - Schuurman, Karianne G.
AU - Helder, Boy
AU - Tas, Sander W.
AU - Schultze, Joachim L.
AU - Hamann, J. rg
AU - Huitinga, Inge
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Case-Control Studies
KW - Female
KW - Gene Expression Profiling/methods
KW - Gene Expression Regulation
KW - Glycolysis/genetics
KW - Gray Matter/metabolism
KW - Humans
KW - Iron/metabolism
KW - Magnetic Resonance Imaging
KW - Male
KW - Membrane Proteins/genetics
KW - Metabolic Networks and Pathways/genetics
KW - Microglia
KW - Microglia/metabolism
KW - Middle Aged
KW - Multiple Sclerosis
KW - Multiple Sclerosis/genetics
KW - Receptors, G-Protein-Coupled/genetics
KW - Receptors, Purinergic P2Y12/genetics
KW - Sequence Analysis, RNA/methods
KW - Transcriptomics
KW - White Matter/metabolism
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062875141&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30867424
UR - http://www.scopus.com/inward/record.url?scp=85062875141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062875141&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-019-08976-7
DO - https://doi.org/10.1038/s41467-019-08976-7
M3 - Article
C2 - 30867424
SN - 2041-1723
VL - 10
SP - 1139
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1139
ER -