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

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[1] The Salk Institute for Biological Studies,Systems Neurobiology Laboratories
[2] University of California Los Angeles,UCLA Brain Research and Artificial Intelligence Nexus, Department of Neurobiology, David Geffen School of Medicine
[3] The Salk Institute for Biological Studies,Genomic Analysis Laboratory
[4] The Salk Institute for Biological Studies,Howard Hughes Medical Institute
[5] Allen Institute for Brain Science,Department of Neurobiology
[6] Cold Spring Harbor Laboratory,Department of Molecular and Cell Biology
[7] Duke University School of Medicine,Helen Wills Neuroscience Institute
[8] University of California Berkeley,Center for Epigenomics, Department of Cellular and Molecular Medicine
[9] University of California Berkeley,Department of Neuroscience
[10] University of California San Diego School of Medicine,Center for Neuroscience and Artificial Intelligence
[11] Ludwig Institute for Cancer Research,Institute for Genome Sciences
[12] Baylor College of Medicine,Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Physics
[13] Baylor College of Medicine,Center for Neural Informatics, Krasnow Institute for Advanced Study
[14] University of Maryland School of Medicine,Bioengineering Department
[15] Harvard University,Computational Neurobiology Laboratory
[16] George Mason University,McGovern Institute for Brain Research
[17] George Mason University,Department of Brain and Cognitive Sciences
[18] The Salk Institute for Biological Studies,Stanley Center for Psychiatric Research
[19] Sanford Burnham Prebys Medical Discovery Institute,Department of Radiology
[20] Massachusetts Institute of Technology,Department of Otorhinolaryngology, Anatomy and Neurobiology
[21] Massachusetts Institute of Technology,Division of Biological Science, Neurobiology Section
[22] Broad Institute of MIT and Harvard,Department of Neurosciences
[23] University of Pennsylvania,Pittsburgh Supercomputing Center
[24] Massachusetts Institute of Technology,Klarman Cell Observatory and Data Sciences Platform
[25] Dartmouth College,Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behaviors
[26] University of Maryland School of Medicine,Department of Psychiatry and Biobehavioral Science, David Geffen School of Medicine
[27] University of California San Diego,Department of Bioengineering
[28] University of California San Diego,Institute for Ophthalmic Research
[29] SciCrunch,Center for Integrative Neuroscience
[30] Inc.,Institute for Bioinformatics and Medical Informatics
[31] California Institute of Technology,Bernstein Center for Computational Neuroscience
[32] Carnegie Mellon University,Department of Physiology and Biophysics
[33] Broad Institute of MIT and Harvard,Division of Biological Sciences
[34] University of California Los Angeles,Department of Cognitive Science
[35] University of California Los Angeles,School of Pharmaceutical Sciences
[36] University of California San Diego,Department of Physics
[37] University of Tübingen,Bioinformatics and Systems Biology Graduate Program
[38] University of Tübingen,Department of Genetics
[39] University of Tübingen,Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics
[40] University of Tübingen,Department of Laboratory Medicine and Pathology
[41] University of Washington,Biomedical Sciences Program, School of Medicine
[42] University of California San Diego,Howard Hughes Medical Institute, Department of Biology
[43] University of California San Diego,Flow Cytometry Core Facility
[44] Tsinghua University,Peptide Biology Laboratories
[45] University of California San Diego,Molecular Neurobiology Laboratory
[46] University of California San Diego,Stanley Institute for Cognitive Genomics
[47] Broad Institute of MIT and Harvard,Department of Statistics and Division of Biostatistics
[48] Harvard Medical School,Department of Biomedical Informatics
[49] Karolinska Institute,Department of Statistics
[50] University of Washington,Department of Statistical Sciences
来源
Nature | 2021年 / 598卷
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摘要
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.
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页码:86 / 102
页数:16
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