Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion.

Nature Neuroscience
Yubin HuangBo Peng

Abstract

Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis. With different transgenic mouse lines, we then demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). Despite a transient pattern of nestin expression in newly forming microglia, none of repopulated microglia were derived from nestin-positive non-microglial cells. In summary, we conclude that repopulated microglia are solely derived from residual microglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.

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Datasets Mentioned

BETA
AF568
AB150067
GSE108269
GSE108416

Methods Mentioned

BETA
transgenic
ELISA
fluorescence-activated cell sorting
RNA-seq
FACS
density gradient centrifugation
scRNA-seq
enzyme-linked immunosorbent assay

Software Mentioned

STAR aligner
HISAT2
ZEN
GraphPad
Cellranger mkfastq
Cell Ranger
FlowJo
Cellranger
Prism
ImageJ

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