[PDF][PDF] White matter aging drives microglial diversity

S Safaiyan, S Besson-Girard, T Kaya… - Neuron, 2021 - cell.com
Neuron, 2021cell.com
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 …
Summary
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.
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