SummaryThe 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.

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) RAPIDO collaborative investigators; Bahadoer

The mammalian nervous system executes complex behaviors controlled by specialised, 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 several distinct, regionally restricted, astrocytes types, which 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.

The brain emerges from the primitive ectoderm as a sheet of neuroepithelial cells which folds into the neural tube during neurulation 1 . The developing nervous system is unique for the length of the developmental window, the extent of the interplay between different anatomical regions and lineages, and the diversity of cell types generated. Therefore, the ability of single-cell RNA-seq to disentangle the molecular heterogeneity of a complex cell pool has been particularly useful to study nervous system development [2][3][4][5][6][7][8][9][10] . Recent studies have shed light on the developing telencephalon 5,11 , the hippocampus 9,12,13 , the developing ventral midbrain 14-16, the developing spinal cord and cerebellum 17,18 , and the hypothalamic arcuate nucleus and diencephalon 19,20 . Single-cell RNA-seq has elucidated the differences between embryonic, postnatal and adult neural progenitors 9,21,22 , and compared normal glial progenitors with their malignant counterparts 23,24 .To map mouse brain development in detail, we collected embryonic brain tissue from 43 pregnant CD-1 mice, sampling each day from E7 to E18 (Extended Data Figure 1a-b, Table S1). We prepared 105 samples by droplet-based single-cell RNA sequencing. After removing low-quality cells and doublets (Methods), 96 samples remained with a mean of 5 766 transcripts (unique molecular identifiers, UMIs) and 1 934 genes detected per cell (Extended Data Figure 1c-f). The total cellular RNA content dropped as a function of

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