Imperial College London
Alternate

Professor Richard Reynolds, BSc AKC PhD

Faculty of Medicine, Department of Brain Sciences

Professor of Cellular Neurobiology
 
 
 
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Contact

 

+44 (0)20 7594 6668r.reynolds

 
 
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Location

 

E414Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Elkjaer:2019:10.1186/s40478-019-0855-7,
author = {Elkjaer, ML and Frisch, T and Reynolds, R and Kacprowski, T and Burton, M and Kruse, TA and Thomassen, M and Baumbach, J and Illes, Z},
doi = {10.1186/s40478-019-0855-7},
journal = {Acta Neuropathologica Communications},
title = {Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis},
url = {http://dx.doi.org/10.1186/s40478-019-0855-7},
volume = {7},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Compared to 25 WM controls, 6713 out of 18,609 genes were significantly differentially expressed in MS tissues (FDR < 0.05). A computational systems medicine analysis was performed to describe the MS lesion endophenotypes. The cellular source of specific molecules was examined by RNAscope, immunohistochemistry, and immunofluorescence. To examine common lesion specific mechanisms, we performed de novo network enrichment based on shared differentially expressed genes (DEGs), and found TGFβ-R2 as a central hub. RNAscope revealed astrocytes as the cellular source of TGFβ-R2 in remyelinating lesions. Since lesion-specific unique DEGs were more common than shared signatures, we examined lesion-specific pathways and de novo networks enriched with unique DEGs. Such network analysis indicated classic inflammatory responses in active lesions; catabolic and heat shock protein responses in inactive lesions; neuronal/axonal specific processes in chronic active lesions. In remyelinating lesions, de novo analyses identified axonal transport responses and adaptive immune markers, which was also supported by the most heterogeneous immunoglobulin gene expression. The signature of the normal-appearing white matter (NAWM) was more similar to control WM than to lesions: only 465 DEGs differentiated NAWM from controls, and 16 were unique. The upregulated marker CD26/DPP4 was expressed by microglia in the NAWM but by mononuclear cells in active lesions, which may indicate a special subset of microglia before the lesion develops, but also emphasizes that omics related to MS lesions should be interpreted in the context of different lesions types. While chronic active lesions were the most distinct from control WM based on the highest number of unique DEGs (n&thi
AU  - Elkjaer,ML
AU  - Frisch,T
AU  - Reynolds,R
AU  - Kacprowski,T
AU  - Burton,M
AU  - Kruse,TA
AU  - Thomassen,M
AU  - Baumbach,J
AU  - Illes,Z
DO  - 10.1186/s40478-019-0855-7
PY  - 2019///
SN  - 2051-5960
TI  - Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis
T2  - Acta Neuropathologica Communications
UR  - http://dx.doi.org/10.1186/s40478-019-0855-7
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31829262
UR  - http://hdl.handle.net/10044/1/76252
VL  - 7
ER  -
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