Molecular Architecture of the Mouse Nervous System

Summary

The mammalian nervous system executes complex behaviors controlled by specialized, precisely positioned, and interacting cell types. Here, we used RNA sequencing of half a million single cells to create a detailed census of cell types in the mouse nervous system. We mapped cell types spatially and derived a hierarchical, data-driven taxonomy. Neurons were the most diverse and were grouped by developmental anatomical units and by the expression of neurotransmitters and neuropeptides. Neuronal diversity was driven by genes encoding cell identity, synaptic connectivity, neurotransmission, and membrane conductance. We discovered seven distinct, regionally restricted astrocyte types that obeyed developmental boundaries and correlated with the spatial distribution of key glutamate and glycine neurotransmitters. In contrast, oligodendrocytes showed a loss of regional identity followed by a secondary diversification. The resource presented here lays a solid foundation for understanding the molecular architecture of the mammalian nervous system and enables genetic manipulation of specific cell types.

Graphical Abstract

Highlights

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  Systematic survey of transcriptomic cell types in the mouse nervous system

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  Taxonomy and hierarchical organization of molecular cell types

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  Seven distinct astrocyte types with regionally restricted distribution

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  Neuronal diversity is similar across brain regions

Abstract

Single-cell transcriptional profiling of the adult mouse nervous system uncovers new cell classes and types across regions, providing a clearer picture of cell diversity by region and a reference atlas for studying the mammalian nervous system.