Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Transcriptomic changes in brain disease.


  1. 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. 2.

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

    CAS  Article  Google Scholar 

  3. 3.

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

    CAS  Article  Google Scholar 

  4. 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).

    CAS  Article  Google Scholar 

  5. 5.

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

    CAS  Article  Google Scholar 

  6. 6.

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

    CAS  Article  Google Scholar 

  7. 7.

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

    Article  Google Scholar 

  8. 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. 9.

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

    CAS  Article  Google Scholar 

  10. 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).

    CAS  Article  Google Scholar 

Download references


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

Author information



Corresponding author

Correspondence to Marco Colonna.

Ethics declarations

Competing interests

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing