Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease
Non-cell autonomous mechanisms are involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), an adult neurodegenerative disease characterized by selective motor neuron loss. While the emerging role of glial cells in ALS has been noted, the detailed cell-type-specific role of glial cells h...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.1045647/full |
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| author | Hirofumi Yamashita Hirofumi Yamashita Hirofumi Yamashita Okiru Komine Noriko Fujimori-Tonou Koji Yamanaka Koji Yamanaka Koji Yamanaka |
| author_facet | Hirofumi Yamashita Hirofumi Yamashita Hirofumi Yamashita Okiru Komine Noriko Fujimori-Tonou Koji Yamanaka Koji Yamanaka Koji Yamanaka |
| author_sort | Hirofumi Yamashita |
| collection | DOAJ |
| description | Non-cell autonomous mechanisms are involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), an adult neurodegenerative disease characterized by selective motor neuron loss. While the emerging role of glial cells in ALS has been noted, the detailed cell-type-specific role of glial cells has not been clarified. Here, we examined mRNA expression changes using microarrays of the spinal cords of three distinct lines of mutant superoxide dismutase (SOD) 1 transgenic mice, an established ALS model. Our analysis used a transcriptome database of component cell types in the central nervous system (CNS), as well as SOD1G93A cell-type transcriptomes. More than half of the differentially expressed genes (DEGs) were highly expressed in microglia, and enrichment analysis of DEGs revealed that immunological reactions were profoundly involved and some transcription factors were upregulated. Our analysis focused on DEGs that are highly expressed in each cell type, as well as chemokines, caspases, and heat shock proteins. Disease-associated microglial genes were upregulated, while homeostatic microglial genes were not, and galectin-3 (Mac2), a known activated microglial marker, was predicted to be ectopically expressed in astrocytes in mutant SOD1 mice. In mutant SOD1 mice, we developed a prediction model for the pathophysiology of different cell types related to TREM2, apolipoprotein E, and lipoproteins. Our analysis offers a viable resource to understand not only the molecular pathologies of each CNS constituent cell type, but also the cellular crosstalk between different cell types under both physiological and pathological conditions in model mice for various neurodegenerative diseases. |
| first_indexed | 2024-04-09T23:50:11Z |
| format | Article |
| id | doaj.art-5b9e12e4b5d946dbbad431bfb450bea9 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T23:50:11Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-5b9e12e4b5d946dbbad431bfb450bea92023-03-17T12:28:04ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-01-011610.3389/fncel.2022.10456471045647Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in diseaseHirofumi Yamashita0Hirofumi Yamashita1Hirofumi Yamashita2Okiru Komine3Noriko Fujimori-Tonou4Koji Yamanaka5Koji Yamanaka6Koji Yamanaka7Department of Neurology, Japanese Red Cross Wakayama Medical Center, Wakayama, JapanDepartment of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanSupport Unit for Bio-Material Analysis, RRD, RIKEN Center for Brain Science, Wako, JapanDepartment of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, JapanDepartment of Neuroscience and Pathobiology, Nagoya University Graduate School of Medicine, Nagoya University, Nagoya, JapanInstitute for Glyco-Core Research (iGCORE), Nagoya University, Nagoya, JapanNon-cell autonomous mechanisms are involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), an adult neurodegenerative disease characterized by selective motor neuron loss. While the emerging role of glial cells in ALS has been noted, the detailed cell-type-specific role of glial cells has not been clarified. Here, we examined mRNA expression changes using microarrays of the spinal cords of three distinct lines of mutant superoxide dismutase (SOD) 1 transgenic mice, an established ALS model. Our analysis used a transcriptome database of component cell types in the central nervous system (CNS), as well as SOD1G93A cell-type transcriptomes. More than half of the differentially expressed genes (DEGs) were highly expressed in microglia, and enrichment analysis of DEGs revealed that immunological reactions were profoundly involved and some transcription factors were upregulated. Our analysis focused on DEGs that are highly expressed in each cell type, as well as chemokines, caspases, and heat shock proteins. Disease-associated microglial genes were upregulated, while homeostatic microglial genes were not, and galectin-3 (Mac2), a known activated microglial marker, was predicted to be ectopically expressed in astrocytes in mutant SOD1 mice. In mutant SOD1 mice, we developed a prediction model for the pathophysiology of different cell types related to TREM2, apolipoprotein E, and lipoproteins. Our analysis offers a viable resource to understand not only the molecular pathologies of each CNS constituent cell type, but also the cellular crosstalk between different cell types under both physiological and pathological conditions in model mice for various neurodegenerative diseases.https://www.frontiersin.org/articles/10.3389/fncel.2022.1045647/fulltranscriptomeamyotrophic lateral sclerosismicroarrayneurodegenerationastrocytesmicroglia |
| spellingShingle | Hirofumi Yamashita Hirofumi Yamashita Hirofumi Yamashita Okiru Komine Noriko Fujimori-Tonou Koji Yamanaka Koji Yamanaka Koji Yamanaka Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease Frontiers in Cellular Neuroscience transcriptome amyotrophic lateral sclerosis microarray neurodegeneration astrocytes microglia |
| title | Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease |
| title_full | Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease |
| title_fullStr | Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease |
| title_full_unstemmed | Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease |
| title_short | Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease |
| title_sort | comprehensive expression analysis with cell type specific transcriptome in als linked mutant sod1 mice revisiting the active role of glial cells in disease |
| topic | transcriptome amyotrophic lateral sclerosis microarray neurodegeneration astrocytes microglia |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.1045647/full |
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