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[210401 저널발표] White matter aging drives microglial diversity

Kyujin Suh │ 2021-03-31

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Journal home page for Neuron

Article
White matter aging drives microglial diversity

Highlights

scRNA-seq identifies age-dependent white matter-associated microglia (WAMs)

WAMs form nodules that are engaged in clearing degenerated myelin

WAM formation depends on TREM2 but not on APOE signaling

In mouse models of Alzheimer’s disease, the WAM response occurs before DAM

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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