Journal
NATURE NEUROSCIENCE
Volume 21, Issue 4, Pages 530-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0090-8
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Funding
- National Key R&D Program of China [2017YFC0111202]
- National Natural Science Foundation of China [31600839]
- Shenzhen Science and Technology Research Program [JCYJ20170307171222692]
- Guangdong Innovative and Entrepreneurial Research Team Program [2013S046]
- Shenzhen Peacock Plan
- NSFC [31771215, 81501164, 81611130224]
- CAST
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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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