Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave
Microglia, the brain's resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using a prolonged colony-stimulating factor 1 receptor inhibitor (CSF1Ri) approach, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from the subventricular zone and associated white matter areas. Following CSF1Ri, these amoeboid cells migrate radially and tangentially in a dynamic wave filling the brain in a distinct pattern, to replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit similar phenotypic and transcriptional profiles to white matter-associated microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into repopulating microglia function and dynamics in the mouse brain.
Sequencing data have been deposited in GEO under accession code GSE166092, and can be explored in an interactive fashion at http://rnaseq.mind.uci.edu/green/. All other data generated or analysed during this study are included in the manuscript and support files.
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic waveNCBI Gene Expression Omnibus, GSE166092.
Article and author information
National Institute of Neurological Disorders and Stroke (R01NS083801)
- Kim N Green
National Institute on Aging (R01AG056768)
- Kim N Green
National Institute on Aging (P50AG016573)
- Kim N Green
National Institute of Neurological Disorders and Stroke (F31NS108611)
- Joshua Crapser
National Institute of Neurological Disorders and Stroke (T32NS082174)
- Yasamine Ghorbanian
Alzheimer's Association (AARF-16-442762)
- Lindsay A Hohsfield
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All rodent experiments were performed in accordance with animal protocols approved (AUP-17-179) by the Institutional Animal Care and Use Committee at the University of California, Irvine (UCI).
- Jaime Grutzendler, Yale University, United States
- Received: January 20, 2021
- Preprint posted: February 18, 2021 (view preprint)
- Accepted: August 22, 2021
- Accepted Manuscript published: August 23, 2021 (version 1)
- Version of Record published: September 8, 2021 (version 2)
© 2021, Hohsfield et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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