White matter aging drives microglial diversity
Trem2
Aging
metabolism [Myelin Sheath]
genetics [Alzheimer Disease]
biosynthesis [Membrane Glycoproteins]
growth & development [White Matter]
Mice
03 medical and health sciences
Trem2 protein, mouse
Apolipoproteins E
genetics [Membrane Glycoproteins]
Alzheimer Disease
physiology [Signal Transduction]
genetics [Receptors, Immunologic]
Animals
ddc:610
Gray Matter
Receptors, Immunologic
microglia, aging
Myelin Sheath
Mice, Knockout
0303 health sciences
Membrane Glycoproteins
cytology [White Matter]
Sequence Analysis, RNA
growth & development [Gray Matter]
cytology [Gray Matter]
physiology [Aging]
Immunohistochemistry
White Matter
physiology [Microglia]
Mice, Inbred C57BL
ultrastructure [Microglia]
biosynthesis [Receptors, Immunologic]
myelin
Gene Expression Regulation
genetics [Apolipoproteins E]
Microglia
Single-Cell Analysis
pathology [Demyelinating Diseases]
white matter
ApoE
Demyelinating Diseases
Signal Transduction
DOI:
10.1016/j.neuron.2021.01.027
Publication Date:
2021-02-19T04:54:50Z
AUTHORS (16)
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (82)
CITATIONS (305)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....