Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Abstract

The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.

Current best practices in single‐cell RNA‐seq analysis: a tutorial

“…Clusters can be annotated by comparing marker genes from the dataset and marker genes from reference dataset via enrichment tests, the Jaccard index or other overlap statistics. Reference webtools such as http://www.mousebrain.org (Zeisel et al , ) or http://dropviz.org/ (Saunders et al , ) allow users to visualize the expression of dataset marker genes in the reference dataset to facilitate cell‐identity annotation.…”

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

“…Thus, more than 500 molecularly distinct classes of neurons and glial cells have been identified in the mouse brain [1,2], and information about the cellular composition of specific brain regions is increasing rapidly [2][3][4][5][6][7][8]. In addition, there is an even larger number of supporting glial cells, i.e., astrocytes and oligodendrocytes, the latter forming myelin sheets around neurons and making up a large part of the white matter in the brain.…”

Don't forget astrocytes when targeting Alzheimer's disease

“…Analysis of astrocyte transcriptome data from the aged mouse in different brain regions however suggests that any difference is more likely species-dependent (Boisvert, Erikson, Shokhirev, & Allen, 2018;Clarke et al, 2018). More recent single-cell transcriptome analyses show that many NMDA receptor transcripts are indeed highly expressed by individual astrocytes in particular brain regions (Saunders et al, 2018). Grin2c, for instance, is highly localized to astrocytes in the posterior cortex and striatum, while Grin2b is more equally expressed by other cell types in the same brain regions.…”