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. Here, Marco Colonna and Simone Brioschi highlight several key papers from 2019 that used single-cell and single-nucleus RNA sequencing to provide exciting insights into the neuro-immune interactions that occur in the healthy and diseased brain. 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.