Molecular Architecture of the Mouse Nervous System

TLDR

The mammalian nervous system executes complex behaviors controlled by specialized, precisely positioned, and interacting cell types. The study mapped cell types spatially and derived a hierarchical, data‑driven taxonomy of the mouse nervous system. RNA sequencing of half a million single cells was used to create a detailed census of cell types in the mouse nervous system. Neurons were the most diverse, grouped by developmental units and neurotransmitter expression, with diversity driven by genes for identity, connectivity, neurotransmission, and membrane conductance; seven regionally restricted astrocyte types were identified, while oligodendrocytes lost regional identity before diversifying; the resource provides a foundation for understanding molecular architecture and enabling targeted genetic manipulation.

Abstract

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.