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 microgl...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/112677 https://orcid.org/0000-0001-5842-5245 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0003-1262-0592 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 |
| author_sort | Hemberg, Martin |
| collection | MIT |
| 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. 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. |
| first_indexed | 2024-09-23T09:55:33Z |
| format | Article |
| id | mit-1721.1/112677 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:55:33Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1126772022-09-30T17:47:02Z Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution 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 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 Mathys, Hansruedi Adaikkan, Chinnakkaruppan Gao, Fan Young, Jennie Zin-Ney Manet, Elodie Regev, Aviv Tsai, Li-Huei 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. National Institutes of Health (U.S.) (Grant RF1 AG054321) 2017-12-11T14:36:13Z 2017-12-11T14:36:13Z 2017-10 2017-08 2017-12-11T12:47:54Z Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/112677 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) https://orcid.org/0000-0001-5842-5245 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0003-1262-0592 http://dx.doi.org/10.1016/j.celrep.2017.09.039 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | 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 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 |
| url | http://hdl.handle.net/1721.1/112677 https://orcid.org/0000-0001-5842-5245 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0003-1262-0592 |
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