@article{671b4ceabbe249ab8d93e96f17bbc70a,
title = "Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes",
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 = "activation, brain, demyelination, development, diversity, glia, heterogeneity, injury, microglia, single-cell RNA seq",
author = "Hammond, {Timothy R.} and Connor Dufort and Lasse Dissing-Olesen and Stefanie Giera and Adam Young and Alec Wysoker and Walker, {Alec J.} and Frederick Gergits and Michael Segel and James Nemesh and Marsh, {Samuel E.} and Arpiar Saunders and Evan Macosko and Florent Ginhoux and Jinmiao Chen and Franklin, {Robin J.M.} and Xianhua Piao and McCarroll, {Steven A.} and Beth Stevens",
note = "Funding Information: We would like to thank Dr. Richard Ransohoff, Dr. Christina Usher, and Dr. Daisy Robinton for their critical feedback and insight while preparing the manuscript. We would like to thank Jon Hammond for developing the website and searchable dataset ( www.microgliasinglecell.com ). This work was funded by grants from the Simons Foundation/SFARI (# 346197 to S.A.M. and B.S.), Rettsyndrome.org mentored fellowship training award (# 3214 to T.R.H.), Silvio O. Conte Center (NIH # P50MH112491 to B.S. and S.A.M.), Stanley Center for Psychiatric Research at the Broad Institute (B.S. and S.A.M.), Helen Hay Whitney Fellowship (A.S.), and Lundbeck Foundation International Postdoc Fellowships (L.D.-O.). Funding Information: We would like to thank Dr. Richard Ransohoff, Dr. Christina Usher, and Dr. Daisy Robinton for their critical feedback and insight while preparing the manuscript. We would like to thank Jon Hammond for developing the website and searchable dataset (www.microgliasinglecell.com). This work was funded by grants from the Simons Foundation/SFARI (#346197 to S.A.M. and B.S.), Rettsyndrome.org mentored fellowship training award (#3214 to T.R.H.), Silvio O. Conte Center (NIH #P50MH112491 to B.S. and S.A.M.), Stanley Center for Psychiatric Research at the Broad Institute (B.S. and S.A.M.), Helen Hay Whitney Fellowship (A.S.), and Lundbeck Foundation International Postdoc Fellowships (L.D.-O.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "15",
doi = "10.1016/j.immuni.2018.11.004",
language = "English (US)",
volume = "50",
pages = "253--271.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",
}