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| Status |
Public on Jan 01, 2018 |
| Title |
Gene expression profiling of multiple sclerosis pathology identifies early patterns of demyelination surrounding chronic active lesions |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.
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| Overall design |
Microarray was performed on 7 chronic active MS lesions (PL-NAWM and RIM), 8 inactive MS lesions (PL-NAWM and RIM), and white matter (WM) of 10 control donors were included in this study. In total 40 samples were included. Experimental RNA and reference pool RNA input was used for linear amplification and fluorescent labeling
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| Contributor(s) |
Hendrickx DA, vanScheppingen J, vanderPoel M, Bossers K, Schuurman KG, vanEden CG, Hol EM, Hamann J, Huitinga I |
| Citation(s) |
29312322 |
| Submission date |
Dec 12, 2017 |
| Last update date |
Jan 24, 2018 |
| Contact name |
Inge Huitinga |
| E-mail(s) |
i.huitinga@nin.knaw.nl
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| Organization name |
NIN
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| Department |
Neuroimmunology
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| Street address |
meibergdreef 47
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| City |
Amsterdam |
| ZIP/Postal code |
1105 BA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL13497 |
Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA422153 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE108000_RAW.tar |
617.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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