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Neuroinflammation and neurodegeneration in human brain at single-cell resolution


Single-cell RNA sequencing and single-nucleus RNA sequencing have recently provided the opportunity to investigate cellular and molecular aspects of neuro-immune interactions in the brain with unprecedented detail. Here, we highlight the major advances in human neuroimmunology reported this year based on these cutting-edge technologies.

Key advances

  • Single-cell and single-nucleus RNA sequencing (snRNA-seq) using brain tissue from patients with multiple sclerosis revealed multiple distinct subsets of microglia; showed that the excitatory neurons of cortical layers 2-3 are most affected by the disease; and identified a subset of oligodendrocytes that express pro-inflammatory genes.

  • snRNA-seq deconvoluted progressive molecular alterations of various cell types arising during Alzheimer disease and revealed potential gender differences.

  • Epigenetic profiling of single nuclei identified enhancers that control the expression of genes underlying the identity and function of all human brain cells.

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Fig. 1: Transcriptomic changes in brain disease.


  1. Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 560, 185–191 (2018).

    Article  Google Scholar 

  2. Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).

    Article  CAS  Google Scholar 

  3. Saunders, A. et al. Molecular diversity and specializations among the cells of the adult mouse brain. Cell 174, 1015–1030 (2018).

    Article  CAS  Google Scholar 

  4. Hammond, T. R. et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50, 253–271 (2019).

    Article  CAS  Google Scholar 

  5. Masuda, T. et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 566, 388–392 (2019).

    Article  CAS  Google Scholar 

  6. Schirmer, L. et al. Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75–82 (2019).

    Article  CAS  Google Scholar 

  7. Jäkel, S. et al. Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature 566, 543–547 (2019).

    Article  Google Scholar 

  8. Falcão, A. M. et al. Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis. Nat. Med. 24, 1837–1844 (2018).

    Article  Google Scholar 

  9. Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019).

    Article  CAS  Google Scholar 

  10. Nott, A. et al. Cell type-specific enhancer-promoter connectivity maps in the human brain and disease risk association. Science 366, 1134–1139 (2019).

    Article  CAS  Google Scholar 

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We thank A. Swain and S. Gilfillan for helpful suggestions during the preparation of the manuscript.

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Correspondence to Marco Colonna.

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Competing interests

M.C. receives research support from Alector, Amgen and Ono. S.B. declares no competing interests.

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Colonna, M., Brioschi, S. Neuroinflammation and neurodegeneration in human brain at single-cell resolution. Nat Rev Immunol 20, 81–82 (2020).

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