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| Status |
Public on Feb 07, 2020 |
| Title |
Gene expression in spinal cord microglia during demyelination and remyelination following neuroattenuated JHMV infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill-defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus, strain JHMV), we show that depletion of microglia after clearance of virus infection resulted in impaired myelin repair and prolonged clinical disease. Microglia were required only during the early stages of remyelination. Notably, large deposits of extracellular vesiculated myelin and cellular debris were detected in the spinal cords of PLX5622-treated and not control mice, which correlated with decreased numbers of oligodendrocytes in demyelinating lesions in drug-treated mice. Further, gene expression analyses demonstrated differential expression of genes involved in myelin debris clearance, lipid and cholesterol recycling, and promotion of oligodendrocyte function. The results also demonstrate that microglial function could not be compensated by infiltrating macrophages. Together, these results demonstrate key roles for microglia in debris clearance and the initiation of remyelination following infection with a neurotropic coronavirus but are not necessary during later stages of remyelination.
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| Overall design |
We used RNA-seq to analyze FACS-sorted microglia from the spinal cords of mock-infected, as well as 14 and 21 day post-JHMV infection mice, n=4 mice per group.
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| Contributor(s) |
Sariol A, Perlman S |
| Citation missing |
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| Submission date |
Feb 06, 2020 |
| Last update date |
Feb 08, 2020 |
| Contact name |
Alan Jacob Sariol |
| E-mail(s) |
alan-sariol@uiowa.edu
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| Phone |
319-335-7576
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| Organization name |
University of Iowa
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| Department |
Microbiology and Immunology
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| Lab |
Perlman Lab
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| Street address |
2868 Coral Ct., Apt 201
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| City |
Coralville |
| State/province |
IA |
| ZIP/Postal code |
52241 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA605293 |
| SRA |
SRP247618 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144911_14dpi_vs._21dpi_pre-log2.xlsx |
3.4 Mb |
(ftp)(http) |
XLSX |
| GSE144911_All_genes_Mockvs14dpi_and_Mockvs21dpi_prelog2.xlsx |
7.6 Mb |
(ftp)(http) |
XLSX |
| GSE144911_Microglia_DEGs_log2_transformed_FCx2.xlsx |
940.1 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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