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 emp...
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doaj-57a85a00af094a2eb7af5592fc186f1a2021-09-08T13:37:58ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.66738Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic waveLindsay A Hohsfield0https://orcid.org/0000-0002-6018-656XAllison R Najafi1Yasamine Ghorbanian2Neelakshi Soni3Joshua Crapser4Dario X Figueroa Velez5Shan Jiang6Sarah E Royer7Sung Jin Kim8Caden M Henningfield9Aileen Anderson10https://orcid.org/0000-0002-8203-8891Sunil P Gandhi11Ali Mortazavi12Matthew A Inlay13Kim N Green14https://orcid.org/0000-0002-6049-6744Department of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesSue and Bill Gross Stem Cell Research Center, Irvine, United States; Department of Molecular Biology and Biochemistry, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United StatesDepartment of Developmental and Cell Biology, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Sue and Bill Gross Stem Cell Research Center, Irvine, United States; Department of Anatomy and Neurobiology, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United States; Sue and Bill Gross Stem Cell Research Center, Irvine, United States; Department of Anatomy and Neurobiology, Irvine, United States; Department of Physical Medicine & Rehabilitation, University of California, Irvine, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United StatesDepartment of Developmental and Cell Biology, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Sue and Bill Gross Stem Cell Research Center, Irvine, United States; Department of Molecular Biology and Biochemistry, Irvine, United StatesDepartment of Neurobiology and Behavior, Irvine, United States; Institute for Memory Impairments and Neurological Disorders, Irvine, United StatesMicroglia, 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.https://elifesciences.org/articles/66738microgliadepletionCSF1Rrepopulationwhite matter |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lindsay A Hohsfield Allison R Najafi Yasamine Ghorbanian Neelakshi Soni Joshua Crapser Dario X Figueroa Velez Shan Jiang Sarah E Royer Sung Jin Kim Caden M Henningfield Aileen Anderson Sunil P Gandhi Ali Mortazavi Matthew A Inlay Kim N Green |
spellingShingle |
Lindsay A Hohsfield Allison R Najafi Yasamine Ghorbanian Neelakshi Soni Joshua Crapser Dario X Figueroa Velez Shan Jiang Sarah E Royer Sung Jin Kim Caden M Henningfield Aileen Anderson Sunil P Gandhi Ali Mortazavi Matthew A Inlay Kim N Green Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave eLife microglia depletion CSF1R repopulation white matter |
author_facet |
Lindsay A Hohsfield Allison R Najafi Yasamine Ghorbanian Neelakshi Soni Joshua Crapser Dario X Figueroa Velez Shan Jiang Sarah E Royer Sung Jin Kim Caden M Henningfield Aileen Anderson Sunil P Gandhi Ali Mortazavi Matthew A Inlay Kim N Green |
author_sort |
Lindsay A Hohsfield |
title |
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
title_short |
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
title_full |
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
title_fullStr |
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
title_full_unstemmed |
Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
title_sort |
subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-08-01 |
description |
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. |
topic |
microglia depletion CSF1R repopulation white matter |
url |
https://elifesciences.org/articles/66738 |
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