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000157763 0247_ $$2doi$$a10.1016/j.neuron.2021.01.027
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000157763 041__ $$aEnglish
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000157763 1001_ $$0P:(DE-2719)9000734$$aSafaiyani, Shima$$b0
000157763 245__ $$aWhite matter aging drives microglial diversity.
000157763 260__ $$aNew York, NY$$bElsevier$$c2021
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000157763 520__ $$aAging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.
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000157763 650_7 $$2Other$$aApoE
000157763 650_7 $$2Other$$aTrem2
000157763 650_7 $$2Other$$amicroglia, aging
000157763 650_7 $$2Other$$amyelin
000157763 650_7 $$2Other$$awhite matter
000157763 650_7 $$2NLM Chemicals$$aApolipoproteins E
000157763 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000157763 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000157763 650_7 $$2NLM Chemicals$$aTrem2 protein, mouse
000157763 650_2 $$2MeSH$$aAging: physiology
000157763 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000157763 650_2 $$2MeSH$$aAnimals
000157763 650_2 $$2MeSH$$aApolipoproteins E: genetics
000157763 650_2 $$2MeSH$$aDemyelinating Diseases: pathology
000157763 650_2 $$2MeSH$$aGene Expression Regulation
000157763 650_2 $$2MeSH$$aGray Matter: cytology
000157763 650_2 $$2MeSH$$aGray Matter: growth & development
000157763 650_2 $$2MeSH$$aImmunohistochemistry
000157763 650_2 $$2MeSH$$aMembrane Glycoproteins: biosynthesis
000157763 650_2 $$2MeSH$$aMembrane Glycoproteins: genetics
000157763 650_2 $$2MeSH$$aMice
000157763 650_2 $$2MeSH$$aMice, Inbred C57BL
000157763 650_2 $$2MeSH$$aMice, Knockout
000157763 650_2 $$2MeSH$$aMicroglia: physiology
000157763 650_2 $$2MeSH$$aMicroglia: ultrastructure
000157763 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000157763 650_2 $$2MeSH$$aReceptors, Immunologic: biosynthesis
000157763 650_2 $$2MeSH$$aReceptors, Immunologic: genetics
000157763 650_2 $$2MeSH$$aSequence Analysis, RNA
000157763 650_2 $$2MeSH$$aSignal Transduction: physiology
000157763 650_2 $$2MeSH$$aSingle-Cell Analysis
000157763 650_2 $$2MeSH$$aWhite Matter: cytology
000157763 650_2 $$2MeSH$$aWhite Matter: growth & development
000157763 7001_ $$aBesson-Girard, Simon$$b1
000157763 7001_ $$0P:(DE-2719)9000609$$aKaya, Tuğberk$$b2
000157763 7001_ $$0P:(DE-2719)2812590$$aCantuti-Castelvetri, Ludovico$$b3
000157763 7001_ $$aLiu, Lu$$b4
000157763 7001_ $$aJi, Hao$$b5
000157763 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b6
000157763 7001_ $$0P:(DE-2719)9001859$$aGouna, Garyfallia$$b7
000157763 7001_ $$aUsifo, Fumere$$b8
000157763 7001_ $$aKannaiyan, Nirmal$$b9
000157763 7001_ $$aFitzner, Dirk$$b10
000157763 7001_ $$aXiang, Xianyuan$$b11
000157763 7001_ $$aRossner, Moritz J$$b12
000157763 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b13
000157763 7001_ $$0P:(DE-2719)9002754$$aGökce, Ozgun$$b14$$udzne
000157763 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b15$$eLast author
000157763 773__ $$0PERI:(DE-600)2001944-0$$a10.1016/j.neuron.2021.01.027$$gVol. 109, no. 7, p. 1100 - 1117.e10$$n7$$p1100 - 1117.e10$$tNeuron$$v109$$x0896-6273$$y2021
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