Molecular Architecture of the Mouse Nervous System

Molecular Architecture of the Mouse Nervous System

August 9, 2018 | Amit Zeisel, Hannah Hochgerner, Peter Lönnerberg, ..., Patrik Ernfors, Ulrika Marklund, Sten Linnarsson
The study provides a comprehensive survey of the molecular architecture of the adult mouse nervous system using single-cell RNA sequencing (scRNA-seq). The researchers analyzed 19 regions, including the brain, spinal cord, and peripheral nervous system, and identified over 500,000 single cells. They developed a multi-stage analysis pipeline called "cytophag" to mitigate technical artifacts and uncover cell types. The results revealed a hierarchical taxonomy of over 70 named taxa, organized by major class, developmental origin, and neurotransmitter type. Key findings include: 1. **Neuronal Diversity**: Neurons were the most diverse cell type, grouped by developmental anatomical units and neurotransmitter expression. Neuronal diversity was driven by genes encoding cell identity, synaptic connectivity, neurotransmission, and membrane conductance. 2. **Astrocyte Types**: Seven distinct astrocyte types were identified, each with regionally restricted distribution. These astrocytes obeyed developmental boundaries and correlated with the spatial distribution of key neurotransmitters. 3. **Oligodendrocyte Lineage**: The oligodendrocyte lineage showed a loss of regional identity followed by secondary diversification. Oligodendrocytes were dominated by a single cluster in caudal regions, while in rostral regions, they were less prevalent. 4. **Postnatal Neurogenesis**: Signs of ongoing neurogenesis were observed in several regions, including the subventricular zone and dentate gyrus subgranular zone. 5. **Astroependymal Cells**: Diverse astroependymal cell types were identified, including ependymal cells and astrocytes, with distinct molecular and spatial patterns. 6. **Vascular and Neural-Crest-Derived Glia**: The study characterized vascular cells and neural-crest-derived glia, including enteric glia, satellite cells, Schwann cells, and olfactory ensheathing cells. 7. **Peripheral Nervous System**: The peripheral nervous system neurons were segregated from the central nervous system, forming distinct sensory, sympathetic, and enteric subdivisions. The findings provide a detailed reference atlas for studying the mammalian nervous system, enabling genetic manipulation of specific cell types and enhancing our understanding of the molecular architecture of the nervous system.The study provides a comprehensive survey of the molecular architecture of the adult mouse nervous system using single-cell RNA sequencing (scRNA-seq). The researchers analyzed 19 regions, including the brain, spinal cord, and peripheral nervous system, and identified over 500,000 single cells. They developed a multi-stage analysis pipeline called "cytophag" to mitigate technical artifacts and uncover cell types. The results revealed a hierarchical taxonomy of over 70 named taxa, organized by major class, developmental origin, and neurotransmitter type. Key findings include: 1. **Neuronal Diversity**: Neurons were the most diverse cell type, grouped by developmental anatomical units and neurotransmitter expression. Neuronal diversity was driven by genes encoding cell identity, synaptic connectivity, neurotransmission, and membrane conductance. 2. **Astrocyte Types**: Seven distinct astrocyte types were identified, each with regionally restricted distribution. These astrocytes obeyed developmental boundaries and correlated with the spatial distribution of key neurotransmitters. 3. **Oligodendrocyte Lineage**: The oligodendrocyte lineage showed a loss of regional identity followed by secondary diversification. Oligodendrocytes were dominated by a single cluster in caudal regions, while in rostral regions, they were less prevalent. 4. **Postnatal Neurogenesis**: Signs of ongoing neurogenesis were observed in several regions, including the subventricular zone and dentate gyrus subgranular zone. 5. **Astroependymal Cells**: Diverse astroependymal cell types were identified, including ependymal cells and astrocytes, with distinct molecular and spatial patterns. 6. **Vascular and Neural-Crest-Derived Glia**: The study characterized vascular cells and neural-crest-derived glia, including enteric glia, satellite cells, Schwann cells, and olfactory ensheathing cells. 7. **Peripheral Nervous System**: The peripheral nervous system neurons were segregated from the central nervous system, forming distinct sensory, sympathetic, and enteric subdivisions. The findings provide a detailed reference atlas for studying the mammalian nervous system, enabling genetic manipulation of specific cell types and enhancing our understanding of the molecular architecture of the nervous system.
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