New-born 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%). Though with a transient pattern of Nestin expression in newly forming microglia, none of repopulated microglia was 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 for the absence of microglial progenitor cells in the adult brain.
In addition to repopulated brain microglia, we investigated the origins of repopulated microglia in the retina and found that the repopulated retinal microglia were not derived from the residual microglia in the retina. Instead, they had two distinct origins: the center-emerging microglia were derived from residual microglia in the optic nerve and the periphery-emerging microglia were derived from macrophages in the ciliary body/iris. Therefore, we identified novel origins of retinal microglia by using a model of microglial repopulation. Our findings expand the understanding on the origins of microglia in the retina.
Dr. Bo Peng obtained his PhD degree from The University of Hong Kong in 2015. Immediately after he obtained his PhD degree, he joint Shenzhen Institutes of Advanced Technology as a principal investigator and associate professor. In 2019, he moved to Fudan University as a professor. He mainly focused on the origin and function of microglia in the central nervous system, including the brain and retina. So far, he has published peer-reviewed papers in Nature Neuroscience (corresponding author) and Cell Discovery (corresponding author)
Huang Y., Xu Z., Xiong S., Sun F., Qin G., Hu G., Wang J., Zhao L., Zhang C., Liang Y.X., Wu T, Lu Z, Humayun M.S., So K.F., Pan Y., Li N., Yuan T.F., Rao Y., and Peng B. (2018) Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nature Neuroscience 21, 530-540.
Huang Y., Xu Z., Xiong S., Qin G., Sun F., Yang J, Yuan T.F. Zhao L, Wang K, Liang Y.X., Fu L., Wu T, Lu Z, So K.F., Rao Y. and Peng B. (2018) Dual origins of retinal microglia in the model of microglia repopulation. Cell Discovery 4, 9.