A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Autor: Yao Z; Allen Institute for Brain Science, Seattle, WA, USA., Liu H; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Xie F; Department of Physics, University of California, San Diego, La Jolla, CA, USA., Fischer S; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA., Adkins RS; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Aldridge AI; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Ament SA; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Bartlett A; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Behrens MM; Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Van den Berge K; Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Gent, Belgium., Bertagnolli D; Allen Institute for Brain Science, Seattle, WA, USA., de Bézieux HR; Division of Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, CA, USA., Biancalani T; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Booeshaghi AS; California Institute of Technology, Pasadena, CA, USA., Bravo HC; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA., Casper T; Allen Institute for Brain Science, Seattle, WA, USA., Colantuoni C; Johns Hopkins School of Medicine, Department of Neurology, Baltimore, MD, USA.; Johns Hopkins School of Medicine, Department of Neuroscience, Baltimore, MD, USA.; University of Maryland School of Medicine, Institute for Genome Sciences, Baltimore, MD, USA., Crabtree J; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Creasy H; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Crichton K; Allen Institute for Brain Science, Seattle, WA, USA., Crow M; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA., Dee N; Allen Institute for Brain Science, Seattle, WA, USA., Dougherty EL; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Doyle WI; Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA., Dudoit S; Department of Statistics, University of California, Berkeley, Berkeley, CA, USA., Fang R; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, San Diego, CA, USA., Felix V; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Fong O; Allen Institute for Brain Science, Seattle, WA, USA., Giglio M; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Goldy J; Allen Institute for Brain Science, Seattle, WA, USA., Hawrylycz M; Allen Institute for Brain Science, Seattle, WA, USA., Herb BR; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Hertzano R; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.; Department of Otorhinolaryngology, Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA., Hou X; Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Hu Q; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Kancherla J; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA., Kroll M; Allen Institute for Brain Science, Seattle, WA, USA., Lathia K; Allen Institute for Brain Science, Seattle, WA, USA., Li YE; Ludwig Institute for Cancer Research, La Jolla, CA, USA., Lucero JD; Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Luo C; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA., Mahurkar A; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., McMillen D; Allen Institute for Brain Science, Seattle, WA, USA., Nadaf NM; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Nery JR; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Nguyen TN; Allen Institute for Brain Science, Seattle, WA, USA., Niu SY; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Ntranos V; University of California, San Francisco, San Francisco, CA, USA., Orvis J; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Osteen JK; Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Pham T; Allen Institute for Brain Science, Seattle, WA, USA., Pinto-Duarte A; Computational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA., Poirion O; Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Preissl S; Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA., Purdom E; Department of Statistics, University of California, Berkeley, Berkeley, CA, USA., Rimorin C; Allen Institute for Brain Science, Seattle, WA, USA., Risso D; Department of Statistical Sciences, University of Padova, Padova, Italy., Rivkin AC; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA., Smith K; Allen Institute for Brain Science, Seattle, WA, USA., Street K; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Sulc J; Allen Institute for Brain Science, Seattle, WA, USA., Svensson V; California Institute of Technology, Pasadena, CA, USA., Tieu M; Allen Institute for Brain Science, Seattle, WA, USA., Torkelson A; Allen Institute for Brain Science, Seattle, WA, USA., Tung H; Allen Institute for Brain Science, Seattle, WA, USA., Vaishnav ED; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Vanderburg CR; Broad Institute of MIT and Harvard, Cambridge, MA, USA., van Velthoven C; Allen Institute for Brain Science, Seattle, WA, USA., Wang X; Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA., White OR; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA., Huang ZJ; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA., Kharchenko PV; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Pachter L; California Institute of Technology, Pasadena, CA, USA., Ngai J; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Regev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Howard Hughes Medical Institute, Department of Biology, MIT, Cambridge, MA, USA., Tasic B; Allen Institute for Brain Science, Seattle, WA, USA., Welch JD; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA., Gillis J; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA., Macosko EZ; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ren B; Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.; Ludwig Institute for Cancer Research, La Jolla, CA, USA., Ecker JR; Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA., Zeng H; Allen Institute for Brain Science, Seattle, WA, USA. HongkuiZ@alleninstitute.org., Mukamel EA; Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA. emukamel@ucsd.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Oct; Vol. 598 (7879), pp. 103-110. Date of Electronic Publication: 2021 Oct 06.
DOI: 10.1038/s41586-021-03500-8
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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