Nat Neurosci. 2018 Apr;21(4):530-540. doi: 10.1038/s41593-018-0090-8. Epub 2018 Feb 22.
Huang Y1, Xu Z1, Xiong S1, Sun F1, Qin G2, Hu G1, Wang J1,3, Zhao L1, Liang YX4, Wu T1, Lu Z1, Humayun MS5, So KF4,6, Pan Y7, Li N7, Yuan TF8,9, Rao Y10,11, Peng B12.
- 1.Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
- 2.Shanghai Center for Bioinformation Technology, Shanghai, China.
- 3.School of Psychology, Nanjing Normal University, Nanjing, China.
- 4.State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
- 5.Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
- 6.Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
- 7.The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
- 8.Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. email@example.com.
- 9.Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. firstname.lastname@example.org.
- 10.State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. email@example.com.
- 11.School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. firstname.lastname@example.org.
- 12.Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. email@example.com
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 residualmicroglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.