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

doi:10.1038/s41593-018-0090-8

. 2018 Apr;21(4):530-540.

doi: 10.1038/s41593-018-0090-8. Epub 2018 Feb 22.

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

Yubin Huang^#¹, Zhen Xu^#¹, Shanshan Xiong¹, Fangfang Sun¹, Guangrong Qin², Guanglei Hu¹, Jingjing Wang^{1

3}, Lei Zhao¹, Yu-Xiang Liang⁴, Tianzhun Wu¹, Zhonghua Lu¹, Mark S Humayun⁵, Kwok-Fai So^{4

6}, Yihang Pan⁷, Ningning Li⁷, Ti-Fei Yuan^{8

9}, Yanxia Rao^{10

11}, Bo Peng¹²

Affiliations

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. ytf0707@126.com.
⁹ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. ytf0707@126.com.
¹⁰ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. yanxiarao@connect.hku.hk.
¹¹ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. yanxiarao@connect.hku.hk.
¹² Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. bopeng@connect.hku.hk.

^# Contributed equally.

PMID: 29472620
DOI: 10.1038/s41593-018-0090-8

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

Yubin Huang et al. Nat Neurosci. 2018 Apr.

. 2018 Apr;21(4):530-540.

doi: 10.1038/s41593-018-0090-8. Epub 2018 Feb 22.

Authors

Affiliations

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. ytf0707@126.com.
⁹ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. ytf0707@126.com.
¹⁰ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. yanxiarao@connect.hku.hk.
¹¹ School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. yanxiarao@connect.hku.hk.
¹² Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. bopeng@connect.hku.hk.

^# Contributed equally.

PMID: 29472620
DOI: 10.1038/s41593-018-0090-8

Erratum in

Author Correction: Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion.
Huang Y, Xu Z, Xiong S, Sun F, Qin G, Hu G, Wang J, Zhao L, Liang YX, Wu T, Lu Z, Humayun MS, So KF, Pan Y, Li N, Yuan TF, Rao Y, Peng B. Huang Y, et al. Nat Neurosci. 2021 Feb;24(2):288. doi: 10.1038/s41593-020-00760-x. Nat Neurosci. 2021. PMID: 33219354 No abstract available.

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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Comment in

Microglia's heretical self-renewal.
Rossi F, Lewis C. Rossi F, et al. Nat Neurosci. 2018 Apr;21(4):455-456. doi: 10.1038/s41593-018-0123-3. Nat Neurosci. 2018. PMID: 29593318 No abstract available.

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References

1. Kettenmann, H., Hanisch, U. K., Noda, M. & Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91, 461–553 (2011). - DOI
1. del Río Hortega, P. Microglia (Hoeber, New York, 1932).
1. del Río Hortega, P. & Penfield, W. Cerebral cicatrix: the reaction of neuroglia and microglia to brain wounds. Bull. Johns Hopkins Hosp. 41, 278–303 (1927).
1. Prinz, M. & Priller, J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci. 15, 300–312 (2014). - DOI
1. Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K. & Pollard, J. W. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6, e26317 (2011). - DOI

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[1] Kettenmann, H., Hanisch, U. K., Noda, M. & Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91, 461–553 (2011). - DOI

[2] Kettenmann, H., Hanisch, U. K., Noda, M. & Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91, 461–553 (2011). - DOI

[3] del Río Hortega, P. Microglia (Hoeber, New York, 1932).

[4] del Río Hortega, P. Microglia (Hoeber, New York, 1932).

[5] del Río Hortega, P. & Penfield, W. Cerebral cicatrix: the reaction of neuroglia and microglia to brain wounds. Bull. Johns Hopkins Hosp. 41, 278–303 (1927).

[6] del Río Hortega, P. & Penfield, W. Cerebral cicatrix: the reaction of neuroglia and microglia to brain wounds. Bull. Johns Hopkins Hosp. 41, 278–303 (1927).

[7] Prinz, M. & Priller, J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci. 15, 300–312 (2014). - DOI

[8] Prinz, M. & Priller, J. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat. Rev. Neurosci. 15, 300–312 (2014). - DOI

[9] Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K. & Pollard, J. W. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6, e26317 (2011). - DOI

[10] Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K. & Pollard, J. W. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6, e26317 (2011). - DOI

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

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

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