Apr 27, 2019

Unique RNA signature of different lesion types in the brain white matter in progressive multiple sclerosis

Acta Neuropathologica Communications
Maria L ElkjaerZsolt Illes

Abstract

The heterogeneity of multiple sclerosis is reflected by dynamic changes of different lesion types in the brain white matter (WM). To identify potential drivers of this process, we RNA-sequenced 73 WM areas from patients with progressive MS (PMS) and 25 control WM. Lesion endophenotypes were described by a computational systems medicine analysis combined with RNAscope, immunohistochemistry, and immunofluorescence. The signature of the normal-appearing WM (NAWM) was more similar to control WM than to lesions: one of the six upregulated genes in NAWM was CD26/DPP4 expressed by microglia. Chronic active lesions that become prominent in PMS had a signature that were different from all other lesion types, and were differentiated from them by two clusters of 62 differentially expressed genes (DEGs). An upcoming MS biomarker, CHI3L1 was among the top ten upregulated genes in chronic active lesions expressed by astrocytes in the rim. TGFβ-R2 was the central hub in a remyelination-related protein interaction network, and was expressed there by astrocytes. We used de novo networks enriched by unique DEGs to determine lesion-specific pathway regulation, i.e. cellular trafficking and activation in active lesions; healing and immune response...Continue Reading

Mentioned in this Paper

Biological Markers
Immune Response
Immunofluorescence Assay
Biochemical Pathway
Immunohistochemistry
DPP4 protein, human
TGFA protein, human
Genes
DPP4
Regulation of Biological Process

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