Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes
By Timothy R. Hammond, Connor Dufort, Lasse Dissing‐Olesen, Stefanie Giera, Adam M. H. Young, Alec Wysoker, A. Walker, Frederick W. Gergits, Michael Segel, J. Nemesh and 9 more. Immunity, 2018
1,835 citations recorded by the source corpus.
Summary 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. Graphical Abstract Figure. No Caption available. HighlightsMouse microglia are heterogenous cells that are most diverse in the developing brainUnique microglia transcriptional states can be localized to many brain regionsSmall subsets of varied inflammatory microglia found in the aged brainDiverse activated microglia subpopulations found in mouse demyelinated lesions and human MS &NA; Hammond et al. redefine mouse microglia states using single‐cell RNA‐seq and in situ brain mapping. They find that microglia are most diverse in the developing, aged, and injured brain. Using focal demyelination, they show that microglia activation states are transcriptionally and spatially distinct within the lesion environment.
Subfields: Immunology, Neurology
View Paper: https://www.semanticscholar.org/paper/554ab4db356e6c4d73a31fd88ead6f41c99c2cee
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Citations in the corpus
- Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation (2019, background): “5 (52) and suggested that they are ontologically diverse from the YS-derived macrophages (53) and potential progenitors of CAMs (52).”
- Overview of General and Discriminating Markers of Differential Microglia Phenotypes (2020, background): “It is considered along with TMEM119 as one of the most specific microglial markers, expressed only by yolk sac-derived cells (Haynes et al., 2006; Amadio et al., 2014).”
- Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain (2019, background): “…in aging40, ALS41, and AD42, and of microglia subpopulations recently identified in development, aging and disease, including “disease-associated microglia” (DAM)12, “neurodegenerative microglia” (MGnD)11, and microglia clusters revealed by Li et al. (2019) and Hammond et al. (2019)14, 15.”