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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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:	Huang, Z. Josh Osten, Pavel Matho, Katherine Savoia, Stephen An, Xu Galbavy, William Hatfield, Joshua Kim, Gukhan Munoz-Castaneda, Rodrigo Narasimhan, Arun Palaniswamy, Ramesh Banerjee, Samik Huilgol, Dhananjay Huo, Bing-Xing Li, Xu Mitra, Partha P. Kelly, Kathleen Gillis, Jesse Crow, Megan Fischer, Stephan
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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