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A Transcriptomic and Epigenomic Cell Atlas of the Mouse Primary Motor Cortex

Nature(2021)

Allen Institute for Brain Science | Genomic Analysis Laboratory | Department of Physics | Stanley Institute for Cognitive Genomics | Institute for Genome Sciences | Computational Neurobiology Laboratory | Department of Statistics | Division of Biostatistics | Broad Institute of MIT and Harvard | California Institute of Technology | Center for Bioinformatics and Computational Biology | Johns Hopkins School of Medicine | Department of Cognitive Science | Bioinformatics and Systems Biology Graduate Program | Univ Calif San Diego | Department of Biomedical Informatics | Ludwig Institute for Cancer Research | University of California | Department of Statistical Sciences | Howard Hughes Medical Institute | Department of Data Sciences | Cold Spring Harbor Laboratory | Department of Molecular and Cell Biology | Department of Computational Medicine and Bioinformatics

Cited 244|Views167
Abstract
Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain 1 – 3 . With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas—containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities—is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions 4 . We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.
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Key words
Cellular neuroscience,Epigenomics,Gene expression profiling,Molecular neuroscience,Motor cortex,Science,Humanities and Social Sciences,multidisciplinary
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