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The molecular cytoarchitecture of the adult mouse brain.

Nature | 2023

The function of the mammalian brain relies upon the specification and spatial positioning of diversely specialized cell types. Yet, the molecular identities of the cell types and their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas of cell types in each brain structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq1,2-a recently developed spatial transcriptomics method with near-cellular resolution-across the entire mouse brain. Integration of these datasets revealed the cell type composition of each neuroanatomical structure. Cell type diversity was found to be remarkably high in the midbrain, hindbrain and hypothalamus, with most clusters requiring a combination of at least three discrete gene expression markers to uniquely define them. Using these data, we developed a framework for genetically accessing each cell type, comprehensively characterized neuropeptide and neurotransmitter signalling, elucidated region-specific specializations in activity-regulated gene expression and ascertained the heritability enrichment of neurological and psychiatric phenotypes. These data, available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including the construction of new genetic tools and the prioritization of specific cell types and circuits in the study of brain diseases.

Pubmed ID: 38092915 RIS Download

Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: RF1 MH124598
  • Agency: NIMH NIH HHS, United States
    Id: U19 MH114821

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This is a list of tools and resources that we have found mentioned in this publication.


Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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1000 Genomes Project and AWS (tool)

RRID:SCR_008801

A dataset containing the full genomic sequence of 1,700 individuals, freely available for research use. The 1000 Genomes Project is an international research effort coordinated by a consortium of 75 companies and organizations to establish the most detailed catalogue of human genetic variation. The project has grown to 200 terabytes of genomic data including DNA sequenced from more than 1,700 individuals that researchers can now access on AWS for use in disease research free of charge. The dataset containing the full genomic sequence of 1,700 individuals is now available to all via Amazon S3. The data can be found at: http://s3.amazonaws.com/1000genomes The 1000 Genomes Project aims to include the genomes of more than 2,662 individuals from 26 populations around the world, and the NIH will continue to add the remaining genome samples to the data collection this year. Public Data Sets on AWS provide a centralized repository of public data hosted on Amazon Simple Storage Service (Amazon S3). The data can be seamlessly accessed from AWS services such Amazon Elastic Compute Cloud (Amazon EC2) and Amazon Elastic MapReduce (Amazon EMR), which provide organizations with the highly scalable compute resources needed to take advantage of these large data collections. AWS is storing the public data sets at no charge to the community. Researchers pay only for the additional AWS resources they need for further processing or analysis of the data. All 200 TB of the latest 1000 Genomes Project data is available in a publicly available Amazon S3 bucket. You can access the data via simple HTTP requests, or take advantage of the AWS SDKs in languages such as Ruby, Java, Python, .NET and PHP. Researchers can use the Amazon EC2 utility computing service to dive into this data without the usual capital investment required to work with data at this scale. AWS also provides a number of orchestration and automation services to help teams make their research available to others to remix and reuse. Making the data available via a bucket in Amazon S3 also means that customers can crunch the information using Hadoop via Amazon Elastic MapReduce, and take advantage of the growing collection of tools for running bioinformatics job flows, such as CloudBurst and Crossbow.

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ComplexHeatmap (tool)

RRID:SCR_017270

Software package to arrange multiple heatmaps and support various annotation graphics. Used to visualize associations between different sources of data sets and to reveal potential patterns.

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GeneOverlap (tool)

RRID:SCR_018419

Software package to test and visualize gene overlaps. Given two gene lists, tests significance of their overlap in comparison with genomic background.

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Brain Cell Data Viewer (tool)

RRID:SCR_023321

Web application that allows users to view and explore brain cell data. Composed of three, interlinked tabs. GeneExp allows users to plot expression of one or two genes in Slide-seq atlas. SingleCell allows users to plot gene expression in snRNA-seq atlas. CellSpatial shows spatial localization of snRNA-seq cell types in Slide-seq dataset. Used to visualize, interact with, and download data.

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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NeMOarchive (data repository)

RRID:SCR_016152

Data repository specifically focused on storage and dissemination of omic data generated from BRAIN Initiative and related brain research projects. Data repository and archive for BCDC and BICCN project, among others. NeMO data include genomic regions associated with brain abnormalities and disease, transcription factor binding sites and other regulatory elements, transcription activity, levels of cytosine modification, histone modification profiles and chromatin accessibility.

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