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Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution

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 ce...

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Autores principales: Mathys, Hansruedi, Adaikkan, Chinnakkaruppan, Gao, Fan, Young, Jennie Z., Manet, Elodie, Hemberg, Martin, De Jager, Philip L., Ransohoff, Richard M., Regev, Aviv, Tsai, Li-Huei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642107/
https://www.ncbi.nlm.nih.gov/pubmed/29020624
http://dx.doi.org/10.1016/j.celrep.2017.09.039
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author Mathys, Hansruedi
Adaikkan, Chinnakkaruppan
Gao, Fan
Young, Jennie Z.
Manet, Elodie
Hemberg, Martin
De Jager, Philip L.
Ransohoff, Richard M.
Regev, Aviv
Tsai, Li-Huei
author_facet Mathys, Hansruedi
Adaikkan, Chinnakkaruppan
Gao, Fan
Young, Jennie Z.
Manet, Elodie
Hemberg, Martin
De Jager, Philip L.
Ransohoff, Richard M.
Regev, Aviv
Tsai, Li-Huei
author_sort Mathys, Hansruedi
collection PubMed
description 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.
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spelling pubmed-56421072017-10-16 Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution Mathys, Hansruedi Adaikkan, Chinnakkaruppan Gao, Fan Young, Jennie Z. Manet, Elodie Hemberg, Martin De Jager, Philip L. Ransohoff, Richard M. Regev, Aviv Tsai, Li-Huei Cell Rep Article 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. 2017-10-10 /pmc/articles/PMC5642107/ /pubmed/29020624 http://dx.doi.org/10.1016/j.celrep.2017.09.039 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Mathys, Hansruedi
Adaikkan, Chinnakkaruppan
Gao, Fan
Young, Jennie Z.
Manet, Elodie
Hemberg, Martin
De Jager, Philip L.
Ransohoff, Richard M.
Regev, Aviv
Tsai, Li-Huei
Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title_full Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title_fullStr Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title_full_unstemmed Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title_short Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
title_sort temporal tracking of microglia activation in neurodegeneration at single-cell resolution
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642107/
https://www.ncbi.nlm.nih.gov/pubmed/29020624
http://dx.doi.org/10.1016/j.celrep.2017.09.039
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