Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.
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Authors
Hammond, Timothy R
Dufort, Connor
Dissing-Olesen, Lasse
Giera, Stefanie
Young, Adam
Wysoker, Alec
Walker, Alec J
Gergits, Frederick
Segel, Michael
Nemesh, James
Marsh, Samuel E
Saunders, Arpiar
Macosko, Evan
Ginhoux, Florent
Chen, Jinmiao
Franklin, Robin JM
Piao, Xianhua
McCarroll, Steven A
Stevens, Beth
Publication Date
2019-01-15Journal Title
Immunity
ISSN
1074-7613
Publisher
Elsevier BV
Volume
50
Issue
1
Pages
253-271.e6
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., et al. (2019). Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.. Immunity, 50 (1), 253-271.e6. https://doi.org/10.1016/j.immuni.2018.11.004
Abstract
Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we analyzed the RNA expression patterns of more than 76,000 individual microglia in mice during development, in old age, and after brain injury. Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states-including chemokine-enriched inflammatory microglia-persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human multiple sclerosis lesions. These distinct microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.
Keywords
Brain, Microglia, Animals, Mice, Inbred C57BL, Humans, Mice, Multiple Sclerosis, Brain Injuries, Demyelinating Diseases, Sequence Analysis, RNA, Adaptation, Physiological, Cell Differentiation, Aging, Longevity, Single-Cell Analysis
Sponsorship
Medical Research Council (MC_PC_12009)
Identifiers
External DOI: https://doi.org/10.1016/j.immuni.2018.11.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287230
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