Neuroscience

Immunology

Inflammation

Microglia

Medicine

Biology

Nature Neuroscience

Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (&gt;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 (&lt;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. Microglia show remarkable regenerative capacity after acute depletion, which had been thought to be derived from de novo progenitors. Peng and colleagues demonstrate that the newly formed microglia are actually solely derived from residual microglia.

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