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Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes

Author

Listed:
  • Marlijn Poel

    (Netherlands Institute for Neuroscience)

  • Thomas Ulas

    (University of Bonn)

  • Mark R. Mizee

    (Netherlands Institute for Neuroscience)

  • Cheng-Chih Hsiao

    (Amsterdam University Medical Centers, University of Amsterdam)

  • Suzanne S. M. Miedema

    (Netherlands Institute for Neuroscience)

  • Adelia

    (Netherlands Institute for Neuroscience)

  • Karianne G. Schuurman

    (Netherlands Institute for Neuroscience)

  • Boy Helder

    (Amsterdam University Medical Centers, University of Amsterdam
    Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, University of Amsterdam)

  • Sander W. Tas

    (Amsterdam University Medical Centers, University of Amsterdam
    Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Centers, University of Amsterdam)

  • Joachim L. Schultze

    (University of Bonn
    University of Bonn)

  • Jörg Hamann

    (Netherlands Institute for Neuroscience
    Amsterdam University Medical Centers, University of Amsterdam)

  • Inge Huitinga

    (Netherlands Institute for Neuroscience)

Abstract

Here we report the transcriptional profile of human microglia, isolated from normal-appearing grey matter (GM) and white matter (WM) of multiple sclerosis (MS) and non-neurological control donors, to find possible early changes related to MS pathology. Microglia show a clear region-specific profile, indicated by higher expression of type-I interferon genes in GM and higher expression of NF-κB pathway genes in WM. Transcriptional changes in MS microglia also differ between GM and WM. MS WM microglia show increased lipid metabolism gene expression, which relates to MS pathology since active MS lesion-derived microglial nuclei show similar altered gene expression. Microglia from MS GM show increased expression of genes associated with glycolysis and iron homeostasis, possibly reflecting microglia reacting to iron depositions. Except for ADGRG1/GPR56, expression of homeostatic genes, such as P2RY12 and TMEM119, is unaltered in normal-appearing MS tissue, demonstrating overall preservation of microglia homeostatic functions in the initiation phase of MS.

Suggested Citation

  • Marlijn Poel & Thomas Ulas & Mark R. Mizee & Cheng-Chih Hsiao & Suzanne S. M. Miedema & Adelia & Karianne G. Schuurman & Boy Helder & Sander W. Tas & Joachim L. Schultze & Jörg Hamann & Inge Huitinga, 2019. "Transcriptional profiling of human microglia reveals grey–white matter heterogeneity and multiple sclerosis-associated changes," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08976-7
    DOI: 10.1038/s41467-019-08976-7
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    Cited by:

    1. Aletta M. R. Bosch & Marlijn Poel & Nina L. Fransen & Maria C. J. Vincenten & Anneleen M. Bobeldijk & Aldo Jongejan & Hendrik J. Engelenburg & Perry D. Moerland & Joost Smolders & Inge Huitinga & Jörg, 2024. "Profiling of microglia nodules in multiple sclerosis reveals propensity for lesion formation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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