Brain macrophages acquire distinct transcriptomes in multiple sclerosis lesions and normal appearing white matter

Anneke Miedema, Emma Gerrits, Nieske Brouwer, Qiong Jiang, Laura Kracht, Michel Meijer, Erik Nutma, Regina Peferoen-Baert, Anna T. E. Pijnacker, Evelyn M. Wesseling, Marion H. C. Wijering, Hans-Joachim Gabius, Sandra Amor, Bart J. L. Eggen, Susanne M. Kooistra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Multiple sclerosis (MS) is a disease of the central nervous system that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed a stress response in brain macrophages in NAWM and identified specific microglia and macrophage subsets at different stages of demyelinating lesions. We identified both phagocytic/activated microglia and CAM clusters that were associated with various MS lesion types. These overall changes in microglia and macrophages associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination.

Original languageEnglish
Article number8
Number of pages18
JournalActa neuropathologica communications
Volume10
Issue number1
DOIs
Publication statusPublished - 28-Jan-2022

Keywords

  • Multiple sclerosis
  • Brain macrophages
  • Microglia
  • Single-cell RNAseq
  • Normal appearing white matter
  • EXPRESSION
  • MICROGLIA
  • MODULATION
  • REVEALS

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