%0 Journal Article
%A Safaiyani, Shima
%A Besson-Girard, Simon
%A Kaya, Tuğberk
%A Cantuti-Castelvetri, Ludovico
%A Liu, Lu
%A Ji, Hao
%A Schifferer, Martina
%A Gouna, Garyfallia
%A Usifo, Fumere
%A Kannaiyan, Nirmal
%A Fitzner, Dirk
%A Xiang, Xianyuan
%A Rossner, Moritz J
%A Brendel, Matthias
%A Gökce, Ozgun
%A Simons, Mikael
%T White matter aging drives microglial diversity.
%J Neuron
%V 109
%N 7
%@ 0896-6273
%C New York, NY
%I Elsevier
%M DZNE-2021-01220
%P 1100 - 1117.e10
%D 2021
%X Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.
%K Aging: physiology
%K Alzheimer Disease: genetics
%K Animals
%K Apolipoproteins E: genetics
%K Demyelinating Diseases: pathology
%K Gene Expression Regulation
%K Gray Matter: cytology
%K Gray Matter: growth & development
%K Immunohistochemistry
%K Membrane Glycoproteins: biosynthesis
%K Membrane Glycoproteins: genetics
%K Mice
%K Mice, Inbred C57BL
%K Mice, Knockout
%K Microglia: physiology
%K Microglia: ultrastructure
%K Myelin Sheath: metabolism
%K Receptors, Immunologic: biosynthesis
%K Receptors, Immunologic: genetics
%K Sequence Analysis, RNA
%K Signal Transduction: physiology
%K Single-Cell Analysis
%K White Matter: cytology
%K White Matter: growth & development
%K ApoE (Other)
%K Trem2 (Other)
%K microglia, aging (Other)
%K myelin (Other)
%K white matter (Other)
%K Apolipoproteins E (NLM Chemicals)
%K Membrane Glycoproteins (NLM Chemicals)
%K Receptors, Immunologic (NLM Chemicals)
%K Trem2 protein, mouse (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33606969
%R 10.1016/j.neuron.2021.01.027
%U https://pub.dzne.de/record/157763