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Single cell transcriptomic analysis of the lateral hypothalamic area reveals molecularly distinct populations of inhibitory and excitatory neurons

ABSTRACT: We employed a droplet-based single cell RNA-sequencing (scRNA-seq) approach to develop a comprehensive census of molecularly distinct cell types in the mouse lateral hypothalamic area (LHA). In addition to 13 distinct non-neuronal cell populations, we define 15 distinct populations of glutamatergic and 15 distinct populations of GABAergic neurons, including both known and novel cell types. This comprehensive transcriptomic analysis of LHA cell types lays the groundwork for understanding the circuit-level underpinnings of LHA coordination of innate behavior.

ORGANISM(S): Mus musculus

PROVIDER: GSE125065 | GEO | 2019/01/15

REPOSITORIES: GEO

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Project description:In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues. However, these approaches have only been applied to a few brain regions and a comprehensive cell atlas of the whole brain is still missing. Here, we imaged a panel of >1,100 genes in ~10 million cells across the entire adult mouse brain using multiplexed error-robust fluorescence in situ hybridization (MERFISH) and performed spatially resolved, single-cell expression profiling at the whole-transcriptome scale by integrating MERFISH and single-cell RNA-sequencing (scRNA-seq) data. Using this approach, we generated a comprehensive cell atlas of >5,000 transcriptionally distinct cell clusters, belonging to >300 major cell types, in the whole mouse brain with high molecular and spatial resolution. Registration of this atlas to the mouse brain common coordinate framework (CCF) allowed systematic quantifications of the cell-type composition and organization in individual brain regions. We further identified spatial modules characterized by distinct cell-type compositions and spatial gradients featuring gradual changes of cells. Finally, this high-resolution spatial map of cells, each with a transcriptome-wide expression profile, allowed us to infer cell-type-specific interactions between several hundred cell-type pairs and predict molecular (ligand-receptor) basis and functional implications of these cell-cell interactions. These results provide rich insights into the molecular and cellular architecture of the brain and a foundation for future functional investigations of neural circuits and their dysfunction in diseases.

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Single cell transcriptomic analysis of the lateral hypothalamic area reveals molecularly distinct populations of inhibitory and excitatory neurons

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