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

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. Lesion initiation and progression in multiple sclerosis is a dynamic but unclear process. Here, the authors highlight cell type-specific gene sets characterizing the action lesion rims and identify trajectories, predicting how normal-appearing white matter can develop into active and mixed active/inactive lesions.