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| Status |
Public on Mar 27, 2023 |
| Title |
Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination [Trem2KO] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination occurring in these diseases. Here, we present a high-resolution snRNA-seq analysis of gene expression changes across all brain cells in this model. We define signatures of prototypic responses to demyelination and remyelination for each cell type, including anti-stress, anti-oxidant-, metabolic-, hypoxia-, IFN-, and IL-33-driven responses, and validate them at the protein level and in IL-33R-deficient mice. We identify related transcription regulators underpinning these pathways, including STAT3, NF-κB, OLIG1 and MAFB. Furthermore, snRNA- seq data provide novel insights into how various brain cell types connect and interact, defining complex circuitries previously unknown to impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency impacts the oligodendrocyte responses to demyelination. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelination and remyelination.
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| Overall design |
Single nucleus RNA-seq analysis of cortex and corpus callosum from WT and TREM2 knockout mice treated with or without cuprizone. Three experimental groups were set up in each genotype: a) demyelination (5-week CPZ treatment); b) remyelination (5-week CPZ treatment, followed by 2-week regular chow); c) control (regular chow throughout the time course)
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| Contributor(s) |
Zhou Y, Hou J, Swain A, Andhey PS |
| Citation(s) |
36952346 |
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| Submission date |
May 25, 2022 |
| Last update date |
May 09, 2023 |
| Contact name |
Yingyue Zhou |
| E-mail(s) |
[email protected]
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| Organization name |
Washington University in St. Louis
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| Department |
Pathology and Immunology
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| Lab |
Marco Colonna
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| Street address |
425 South Euclid Ave, 8107, 8th floor BJCIH,, Pathology and Immunology
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| City |
Saint Louis |
| State/province |
Missouri |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| GSM6190829 |
cortex and corpus callosum, Normal WT, 1 |
| GSM6190830 |
cortex and corpus callosum, Normal WT, 2 |
| GSM6190831 |
cortex and corpus callosum, Normal Trem2-/-, 1 |
| GSM6190832 |
cortex and corpus callosum, Normal Trem2-/-, 2 |
| GSM6190833 |
cortex and corpus callosum, Remyelination WT, 1 |
| GSM6190834 |
cortex and corpus callosum, Remyelination WT, 2 |
| GSM6190835 |
cortex and corpus callosum, Remyelination WT, 3 |
| GSM6190836 |
cortex and corpus callosum, Remyelination Trem2-/-, 1 |
| GSM6190837 |
cortex and corpus callosum, Remyelination Trem2-/-, 2 |
| GSM6190838 |
cortex and corpus callosum, Remyelination Trem2-/-, 3 |
| GSM6190839 |
cortex and corpus callosum, Demyelination WT, 1 |
| GSM6190840 |
cortex and corpus callosum, Demyelination WT, 2 |
| GSM6190841 |
cortex and corpus callosum, Demyelination WT, 3 |
| GSM6190842 |
cortex and corpus callosum, Demyelination Trem2-/-, 1 |
| GSM6190843 |
cortex and corpus callosum, Demyelination Trem2-/-, 2 |
| GSM6190844 |
cortex and corpus callosum, Demyelination Trem2-/-, 3 |
| GSM6190845 |
cortex and corpus callosum, Normal WT, 3 |
| GSM6190846 |
cortex and corpus callosum, Normal Trem2-/-, 3 |
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| This SubSeries is part of SuperSeries: |
| GSE204770 |
Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination |
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| Relations |
| BioProject |
PRJNA842235 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE204769_RAW.tar |
737.9 Mb |
(http)(custom) |
TAR (of H5) |
| GSE204769_celltype_metadata.tsv.gz |
1.4 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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