A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain

By Arpiar Saunders, Evan Z. Macosko, Alec Wysoker, Melissa Goldman, Fenna M. Krienen, Heather de Rivera, Elizabeth Bien, M. Baum, Shuyu Wang, A. Goeva and 5 more. 2018

27 citations recorded by the source corpus.

The mammalian brain is composed of diverse, specialized cell populations, few of which we fully understand. To more systematically ascertain and learn from cellular specializations in the brain, we used Drop-seq to perform single-cell RNA sequencing of 690,000 cells sampled from nine regions of the adult mouse brain: frontal and posterior cortex (156,000 and 99,000 cells, respectively), hippocampus (113,000), thalamus (89,000), cerebellum (26,000), and all of the basal ganglia – the striatum (77,000), globus pallidus externus/nucleus basalis (66,000), entopeduncular/subthalamic nuclei (19,000), and the substantia nigra/ventral tegmental area (44,000). We developed computational approaches to distinguish biological from technical signals in single-cell data, then identified 565 transcriptionally distinct groups of cells, which we annotate and present through interactive online software we developed for visualizing and re-analyzing these data (DropViz). Comparison of cell classes and types across regions revealed features of brain organization. These included a neuronal gene-expression module for synthesizing axonal and presynaptic components; widely shared patterns in the combinatorial co-deployment of voltage-gated ion channels by diverse neuronal populations; functional distinctions among cells of the brain vasculature; and specialization of glutamatergic neurons across cortical regions to a degree not observed in other neuronal or non-neuronal populations. We describe systematic neuronal classifications for two complex, understudied regions of the basal ganglia, the globus pallidus externus and substantia nigra reticulata. In the striatum, where neuron types have been intensely researched, our data reveal a previously undescribed population of striatal spiny projection neurons (SPNs) comprising 4% of SPNs. The adult mouse brain cell atlas can serve as a reference for analyses of development, disease, and evolution.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Neurology

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Citations in the corpus

The art of using t-SNE for single-cell transcriptomics (2018, background): “…has become possible to obtain gene expression data from tens of thousands of cells using full-length sequencing (Tasic et al., 2017; The Tabula Muris Consortium, 2018) and from hundreds of thousands of cells using tag-based protocols (Zeisel et al., 2018; Han et al., 2018; Saunders et al., 2018).”
Heavy-tailed kernels reveal a finer cluster structure in t-SNE visualisations (2019, background): “, 2013) and transcriptomics (e.g. Tasic et al., 2018; Zeisel et al., 2018; Saunders et al., 2018) where samples are cells and features are proteins or genes, to population genetics (Diaz-Papkovich et al.”
Challenges in unsupervised clustering of single-cell RNA-seq data (2019, background): “For example, several collections of cells, each containing hundreds of thousands of cells from the mouse brain, have recently been released 12–14 , 100 .”
A connectome of the Drosophila central complex reveals network motifs suitable for flexible navigation and context-dependent action selection (2020, background): “Both these features apply to much larger brains as well (Hodge et al., 2019; Maruoka et al., 2017; Saunders et al., 2018; Strange et al., 2014; Tasic et al., 2018), although there is likely greater flexibility in the wiring of mammalian circuits and greater heterogeneity within cell types in the mam”