Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
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 mic...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717313141 |
| _version_ | 1818234049649442816 |
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| author | Hansruedi Mathys Chinnakkaruppan Adaikkan Fan Gao Jennie Z. Young Elodie Manet Martin Hemberg Philip L. De Jager Richard M. Ransohoff Aviv Regev Li-Huei Tsai |
| author_facet | Hansruedi Mathys Chinnakkaruppan Adaikkan Fan Gao Jennie Z. Young Elodie Manet Martin Hemberg Philip L. De Jager Richard M. Ransohoff Aviv Regev Li-Huei Tsai |
| author_sort | Hansruedi Mathys |
| collection | DOAJ |
| description | 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. : 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. Keywords: microglia, Alzheimer’s disease, neurodegeneration, single-cell RNA sequencing |
| first_indexed | 2024-12-12T11:31:54Z |
| format | Article |
| id | doaj.art-4195e716550c4f05a5c202c826c99548 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T11:31:54Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4195e716550c4f05a5c202c826c995482022-12-22T00:25:45ZengElsevierCell Reports2211-12472017-10-01212366380Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell ResolutionHansruedi Mathys0Chinnakkaruppan Adaikkan1Fan Gao2Jennie Z. Young3Elodie Manet4Martin Hemberg5Philip L. De Jager6Richard M. Ransohoff7Aviv Regev8Li-Huei Tsai9Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USAPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USAPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USAPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USAPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USADepartment of Cellular Genetics, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UKCenter for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USABiogen, 225 Binney Street, Cambridge, MA 02142, USABroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02140, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USAPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Corresponding authorSummary: 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. Keywords: microglia, Alzheimer’s disease, neurodegeneration, single-cell RNA sequencinghttp://www.sciencedirect.com/science/article/pii/S2211124717313141 |
| spellingShingle | Hansruedi Mathys Chinnakkaruppan Adaikkan Fan Gao Jennie Z. Young Elodie Manet Martin Hemberg Philip L. De Jager Richard M. Ransohoff Aviv Regev Li-Huei Tsai Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution Cell Reports |
| 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://www.sciencedirect.com/science/article/pii/S2211124717313141 |
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