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A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. Here, we found age-related alterations of oligodendrocytes with a reduction of total oligodendrocyte density in the aging murine white matter. Using single-cell RNA sequencing, we identify interferon-responsive oligodendrocytes, which localize in proximity of CD8+ T cells in the aging white matter. Absence of functional lymphocytes ...

Grey and white matter (corpus callosum) were dissected from the brain of 4 months and 21 months old wild type mice, single cell suspension was isolated using Neural Tissue Dissection kit (myelin was removed on percoll gradient) then microglia cells were isolated using CD11b microbeads by Magnetic separation with MS columns (MACS technology).The cell pellets are resuspended in the RLT buffer (100ul-150ul), snap frozen in liquid nitrogen and stored in -80 freezer. RNA was extracted and transcriptome ...

Aging results in both grey and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and grey matter separately, we identified white matter associated microglia (WAM), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by the activation of genes implicated in phagocytic activity and lipid metabolism. WAM depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and ...

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Creator: Rainer Malik

Submitter: Rainer Malik

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