Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
By H. Mathys, Chinnakkaruppan Adaikkan, Fan Gao, J. Z. Young, Elodie Manet, Martin Hemberg, P. D. De Jager, R. Ransohoff, Aviv Regev, Li-Huei Tsai. Cell Reports, 2017
636 citations recorded by the source corpus.
SUMMARY Microglia, the tissue-resident macrophages in the brain, are damage sensors that react to nearly any perturbation, including neurodegenerative diseases such as Alzheimer’s disease (AD). Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. In this neurodegeneration model, we discovered two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively. Furthermore, our work identified previously unobserved heterogeneity in the response of microglia to neurodegeneration, discovered disease stage-specific microglia cell states, revealed the trajectory of cellular reprogramming of microglia in response to neurodegeneration, and uncovered the underlying transcriptional programs.
Subfields: Immunology, Neurology
View Paper: https://www.semanticscholar.org/paper/759bc4c7eb3751a22b93cf5d5c243157c1749cd8
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Citations in the corpus
- APOE4 Causes Widespread Molecular and Cellular Alterations Associated with Alzheimer’s Disease Phenotypes in Human iPSC-Derived Brain Cell Types (2018, neutral): “Multiple studies show a positive relationship between upregulation of immune-related genes and APOE4 genotype (Keren-Shaul et al., 2017; Mathys et al., 2017).”
- Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes (2018, background): “Therefore, the detection of localized populations of microglia expressing interferon-response genes may assist in identifying foci of neuronal injury or degeneration (Mathys et al., 2017).”
- The Major Risk Factors for Alzheimer’s Disease: Age, Sex, and Genes Modulate the Microglia Response to Aβ Plaques (2019, background): “Microglia expressing interferon response genes have been described as a late response to neurodegeneration in a CK-p25 model (Mathys et al., 2017); however, these look quite different from the IRMs described here.”
- Multi-sensory gamma stimulation ameliorates Alzheimer’s-associated pathology and improves cognition. (2019, background): “…also indicate a range in microglial response that can be elicited by GENUS (Ransohoff and Car-dona, 2010) and is supported by accumulating evidence that microglia are heterogeneous and display a spectrum of activated states (Walker and Lue, 2015; Mathys et al., 2017; Keren-Shaul et al., 2017).”
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “13,14,16 Notably, DAMs were localized near A β plaques and participated in the clearance of β -amyloid.”