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Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Hammond, Timothy R 
Dufort, Connor 
Dissing-Olesen, Lasse 
Giera, Stefanie 
Young, Adam 

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.

Description

Keywords

activation, brain, demyelination, development, diversity, glia, heterogeneity, injury, microglia, single-cell RNA seq, Adaptation, Physiological, Aging, Animals, Brain, Brain Injuries, Cell Differentiation, Demyelinating Diseases, Humans, Longevity, Mice, Mice, Inbred C57BL, Microglia, Multiple Sclerosis, Sequence Analysis, RNA, Single-Cell Analysis

Journal Title

Immunity

Conference Name

Journal ISSN

1074-7613
1097-4180

Volume Title

50

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_PC_12009)