Journal Article

DZNE-2021-01220

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png White matter aging drives microglial diversity.

Safaiyani, S.DZNE* ; Besson-Girard, S. ; Kaya, T.DZNE* ; Cantuti-Castelvetri, L.DZNE* ; Liu, L. ; Ji, H. ; Schifferer, M.DZNE* ; Gouna, G.DZNE* ; Usifo, F. ; Kannaiyan, N. ; Fitzner, D. ; Xiang, X. ; Rossner, M. J. ; Brendel, M.Extern* ; Gökce, O.Extern* ; Simons, M. (Last author)DZNE*

2021
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2021.01.027

Abstract: 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.

Keyword(s): Aging: physiology (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Animals (MeSH) ; Apolipoproteins E: genetics (MeSH) ; Demyelinating Diseases: pathology (MeSH) ; Gene Expression Regulation (MeSH) ; Gray Matter: cytology (MeSH) ; Gray Matter: growth & development (MeSH) ; Immunohistochemistry (MeSH) ; Membrane Glycoproteins: biosynthesis (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Microglia: physiology (MeSH) ; Microglia: ultrastructure (MeSH) ; Myelin Sheath: metabolism (MeSH) ; Receptors, Immunologic: biosynthesis (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Sequence Analysis, RNA (MeSH) ; Signal Transduction: physiology (MeSH) ; Single-Cell Analysis (MeSH) ; White Matter: cytology (MeSH) ; White Matter: growth & development (MeSH) ; ApoE ; Trem2 ; microglia, aging ; myelin ; white matter ; Apolipoproteins E ; Membrane Glycoproteins ; Receptors, Immunologic ; Trem2 protein, mouse

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Contributing Institute(s):

1. Molecular Neurobiology (AG Simons)
2. Neuronal Cell Biology (AG Misgeld)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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