000157763 001__ 157763 000157763 005__ 20240111134154.0 000157763 0247_ $$2doi$$a10.1016/j.neuron.2021.01.027 000157763 0247_ $$2pmid$$apmid:33606969 000157763 0247_ $$2ISSN$$a0896-6273 000157763 0247_ $$2ISSN$$a1097-4199 000157763 0247_ $$2altmetric$$aaltmetric:100394012 000157763 037__ $$aDZNE-2021-01220 000157763 041__ $$aEnglish 000157763 082__ $$a610 000157763 1001_ $$0P:(DE-2719)9000734$$aSafaiyani, Shima$$b0 000157763 245__ $$aWhite matter aging drives microglial diversity. 000157763 260__ $$aNew York, NY$$bElsevier$$c2021 000157763 3367_ $$2DRIVER$$aarticle 000157763 3367_ $$2DataCite$$aOutput Types/Journal article 000157763 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1704976877_10752 000157763 3367_ $$2BibTeX$$aARTICLE 000157763 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000157763 3367_ $$00$$2EndNote$$aJournal Article 000157763 520__ $$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. 000157763 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0 000157763 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 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 - 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