TY  - JOUR
AU  - Safaiyani, Shima
AU  - Besson-Girard, Simon
AU  - Kaya, Tuğberk
AU  - Cantuti-Castelvetri, Ludovico
AU  - Liu, Lu
AU  - Ji, Hao
AU  - Schifferer, Martina
AU  - Gouna, Garyfallia
AU  - Usifo, Fumere
AU  - Kannaiyan, Nirmal
AU  - Fitzner, Dirk
AU  - Xiang, Xianyuan
AU  - Rossner, Moritz J
AU  - Brendel, Matthias
AU  - Gökce, Ozgun
AU  - Simons, Mikael
TI  - White matter aging drives microglial diversity.
JO  - Neuron
VL  - 109
IS  - 7
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2021-01220
SP  - 1100 - 1117.e10
PY  - 2021
AB  - 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.
KW  - Aging: physiology
KW  - Alzheimer Disease: genetics
KW  - Animals
KW  - Apolipoproteins E: genetics
KW  - Demyelinating Diseases: pathology
KW  - Gene Expression Regulation
KW  - Gray Matter: cytology
KW  - Gray Matter: growth & development
KW  - Immunohistochemistry
KW  - Membrane Glycoproteins: biosynthesis
KW  - Membrane Glycoproteins: genetics
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Microglia: physiology
KW  - Microglia: ultrastructure
KW  - Myelin Sheath: metabolism
KW  - Receptors, Immunologic: biosynthesis
KW  - Receptors, Immunologic: genetics
KW  - Sequence Analysis, RNA
KW  - Signal Transduction: physiology
KW  - Single-Cell Analysis
KW  - White Matter: cytology
KW  - White Matter: growth & development
KW  - ApoE (Other)
KW  - Trem2 (Other)
KW  - microglia, aging (Other)
KW  - myelin (Other)
KW  - white matter (Other)
KW  - Apolipoproteins E (NLM Chemicals)
KW  - Membrane Glycoproteins (NLM Chemicals)
KW  - Receptors, Immunologic (NLM Chemicals)
KW  - Trem2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:33606969
DO  - DOI:10.1016/j.neuron.2021.01.027
UR  - https://pub.dzne.de/record/157763
ER  -