Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis

Astrid M Alsema, Marion H C Wijering, Anneke Miedema, Janssen M Kotah, Mirjam Koster, Merel Rijnsburger, Hilmar R J van Weering, Helga E de Vries, Wia Baron, Susanne M Kooistra, Bart J L Eggen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions. Expression changes in astrocyte-specific, oligodendrocyte-specific and microglia-specific gene sets characterize the active lesion rims. Furthermore, we identify three WM lesion progression trajectories, predicting how normal-appearing WM can develop into WM active or mixed active-inactive lesions. Our data shed light on the dynamic progression of MS lesions.

Original languageEnglish
Pages (from-to)2341–2353
Number of pages38
JournalNature neuroscience
Volume27
Early online date5-Nov-2024
DOIs
Publication statusPublished - Dec-2024

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