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

Astrid M Alsema1,2, Marion H C Wijering1,2, Anneke Miedema1,2

  • 1Department of Biomedical Sciences, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Nature Neuroscience
|November 5, 2024
PubMed

Insights

Researchers mapped gene expression in multiple sclerosis (MS) lesions to understand disease progression. They identified distinct gene signatures in active lesions and pathways predicting how normal white matter develops into MS lesions.

Area of Science:

  • Neuroscience
  • Immunology
  • Genomics

Background:

  • Multiple sclerosis (MS) is a central nervous system inflammatory disease.
  • It involves myelin loss and neurodegeneration.
  • Understanding MS lesion initiation and progression is crucial.

Purpose of the Study:

  • To generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions.
  • To identify molecular signatures associated with MS lesion activity and progression.
  • To elucidate the dynamic changes in the central nervous system during MS.

Main Methods:

  • Spatial gene expression mapping of MS lesions in white matter and grey matter.
  • Analysis of gene signatures in different MS lesion types, focusing on active lesion rims.
  • Identification of WM lesion progression trajectories using gene expression data.

Main Results:

  • Distinct gene expression domains were identified in various MS lesion types.
  • Active MS lesion rims showed characteristic expression changes in astrocyte, oligodendrocyte, and microglia genes.
  • Three distinct WM lesion progression trajectories were identified, predicting the evolution of normal-appearing WM.

Conclusions:

  • Spatial gene expression mapping provides insights into MS lesion heterogeneity.
  • Specific gene expression patterns characterize active MS lesion rims and progression.
  • The study elucidates dynamic pathways of MS lesion development in the central nervous system.

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