You are here

Immunity DOI:10.1016/j.immuni.2018.11.004

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

Publication TypeJournal Article
Year of Publication2019
AuthorsHammond, TR, Dufort, C, Dissing-Olesen, L, Giera, S, Young, A, Wysoker, A, Walker, AJ, Gergits, F, Segel, M, Nemesh, J, Marsh, SE, Saunders, A, Macosko, E, Ginhoux, F, Chen, J, Franklin, RJM, Piao, X, McCarroll, SA, Stevens, B
Date Published2019 Jan 15
KeywordsAdaptation, 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

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.


Alternate JournalImmunity
PubMed ID30471926
PubMed Central IDPMC6655561
Grant List / HHMI_ / Howard Hughes Medical Institute / United States
MC_PC_12009 / MRC_ / Medical Research Council / United Kingdom
P50 MH112491 / MH / NIMH NIH HHS / United States