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Peer-reviewedCC BYCell Reports

Microglial states associate with lesion dynamics in multiple sclerosis

  • Aletta M.R. van den Bosch1
  • Jia Hui Khoo2
  • Zhigang Lu2
  • Han Liang2
  • Dennis D. Wever3
  • Li Pu2
  • Bart J. L. Eggen4
  • Mathias Uhlén5
  • Joost Smolders6
  • Jörg Hamann7
  • Zhouchun Shang2
  • Jan Mulder8
1 more authors
  • Inge Huitinga9
9 affiliations
  1. 1Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands. Electronic address: [email protected]
  2. 2BGI Research, Riga, Latvia
  3. 3Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands
  4. 4Section Molecular Neurobiology, Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  5. 5Department of Neuroscience, Karolinska Institute, Stockholm, Sweden; Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden
  6. 6Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands; MS Center ErasMS, Department of Neurology and Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
  7. 7Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands; Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center, Amsterdam, the Netherlands
  8. 8Department of Neuroscience, Karolinska Institute, Stockholm, Sweden. Electronic address: [email protected]
  9. 9Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected]
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Abstract

Multiple sclerosis (MS) is a neuroinflammatory disease of the CNS characterized by demyelinating lesions. Lesion expansion contributes to disability progression, whereas remyelination may restore neurological function. How these divergent outcomes relate to microglial states remains incompletely understood. Using single-cell-resolution spatial transcriptomics, we compare lesions containing foamy to those containing ramified microglia in postmortem human brain tissue. We find distinct cellular and molecular signatures spatially associated with microglial morphology. Lesions with ramified microglia display gene expression profiles associated with myelin stability and axonal support, consistent with an environment permissive for repair. In contrast, lesions with foamy microglia exhibit immune activation, immunoglobulin production, complement activity, iron dysregulation, immune-oligodendrocytes, and demyelination. These findings show that molecular programs linked to lesion pathology are spatially segregated in association with microglial state, indicating distinct immune-glial niches associated with lesion expansion and repair.

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Cite

BibTeXRIS
BibTeX
@article{bosch2026microglial,
  title = {{Microglial states associate with lesion dynamics in multiple sclerosis}},
  author = {Aletta M.R. van den Bosch and Jia Hui Khoo and Zhigang Lu and Han Liang and Dennis D. Wever and Li Pu and Bart J. L. Eggen and Mathias Uhlén and Joost Smolders and Jörg Hamann and Zhouchun Shang and Jan Mulder and Inge Huitinga},
  journal = {Cell Reports},
  year = {2026},
  month = jun,
  doi = {10.1016/j.celrep.2026.117538},
  url = {https://doi.org/10.1016/j.celrep.2026.117538},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Microglial states associate with lesion dynamics in multiple sclerosis
AU  - Aletta M.R. van den Bosch
AU  - Jia Hui Khoo
AU  - Zhigang Lu
AU  - Han Liang
AU  - Dennis D. Wever
AU  - Li Pu
AU  - Bart J. L. Eggen
AU  - Mathias Uhlén
AU  - Joost Smolders
AU  - Jörg Hamann
AU  - Zhouchun Shang
AU  - Jan Mulder
AU  - Inge Huitinga
PY  - 2026
DA  - 2026/06/01
JO  - Cell Reports
DO  - 10.1016/j.celrep.2026.117538
UR  - https://doi.org/10.1016/j.celrep.2026.117538
AB  - Multiple sclerosis (MS) is a neuroinflammatory disease of the CNS characterized by demyelinating lesions. Lesion expansion contributes to disability progression, whereas remyelination may restore neurological function. How these divergent outcomes relate to microglial states remains incompletely understood. Using single-cell-resolution spatial transcriptomics, we compare lesions containing foamy to those containing ramified microglia in postmortem human brain tissue. We find distinct cellular and molecular signatures spatially associated with microglial morphology. Lesions with ramified microglia display gene expression profiles associated with myelin stability and axonal support, consistent with an environment permissive for repair. In contrast, lesions with foamy microglia exhibit immune activation, immunoglobulin production, complement activity, iron dysregulation, immune-oligodendrocytes, and demyelination. These findings show that molecular programs linked to lesion pathology are spatially segregated in association with microglial state, indicating distinct immune-glial niches associated with lesion expansion and repair.
SN  - 2211-1247
SN  - 2639-1856
ER  -