A multimodal cell census and atlas of the mammalian primary motor cortex

BRAIN Initiative Cell Census Network (BICCN) (October 2021) A multimodal cell census and atlas of the mammalian primary motor cortex. Nature, 598 (7879). pp. 86-102. ISSN 0028-0836

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URL: https://www.ncbi.nlm.nih.gov/pubmed/34616075
DOI: 10.1038/s41586-021-03950-0

Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
organism description > animal
Investigative techniques and equipment > brain atlas
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics
organism description > animal > gender > female
organism description > animal > gender
bioinformatics > genomics and proteomics > small molecules > Glutamate
organism description > animal > mammal
organs, tissues, organelles, cell types and functions > tissues types and functions > motor cortex
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions
organism description > animal > mammal > rodent
bioinformatics > genomics and proteomics > small molecules
organs, tissues, organelles, cell types and functions > tissues types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:
Communities: CSHL labs > Huang lab
CSHL labs > Mitra lab
CSHL labs > Osten lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: October 2021
Date Deposited: 27 Oct 2021 18:55
Last Modified: 17 Jan 2024 20:04
PMCID: PMC8494634
URI: https://repository.cshl.edu/id/eprint/40402

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