Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
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Author(s)
Hemberg, Martin
De Jager, Philip L.
Ransohoff, Richard M.
Mathys, Hansruedi
Adaikkan, Chinnakkaruppan
Gao, Fan
Young, Jennie Zin-Ney
Manet, Elodie
Regev, Aviv
Tsai, Li-Huei
Date Issued
October 2017
Journal
Cell Reports
Publisher
Elsevier
Citation
Mathys, Hansruedi et al. “Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution.” Cell Reports 21, 2 (October 2017): 366–380 © 2017 The Author(s)
Version
Final published version
Abstract
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. Mathys et al. use single-cell RNA sequencing to determine the phenotypic heterogeneity of microglia during the progression of neurodegeneration. They identify multiple disease stage-specific cell states, including two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2017.09.039
