Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex.

Autor: Luo C; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Keown CL; Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA., Kurihara L; Swift Biosciences Inc., 58 Parkland Plaza, Suite 100, Ann Arbor, MI 48103, USA., Zhou J; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA., He Y; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA., Li J; Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA., Castanon R; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Lucero J; Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Nery JR; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Sandoval JP; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Bui B; Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Sejnowski TJ; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Harkins TT; Swift Biosciences Inc., 58 Parkland Plaza, Suite 100, Ann Arbor, MI 48103, USA., Mukamel EA; Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu., Behrens MM; Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu., Ecker JR; Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu.; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2017 Aug 11; Vol. 357 (6351), pp. 600-604.
DOI: 10.1126/science.aan3351
Abstrakt: The mammalian brain contains diverse neuronal types, yet we lack single-cell epigenomic assays that are able to identify and characterize them. DNA methylation is a stable epigenetic mark that distinguishes cell types and marks regulatory elements. We generated >6000 methylomes from single neuronal nuclei and used them to identify 16 mouse and 21 human neuronal subpopulations in the frontal cortex. CG and non-CG methylation exhibited cell type-specific distributions, and we identified regulatory elements with differential methylation across neuron types. Methylation signatures identified a layer 6 excitatory neuron subtype and a unique human parvalbumin-expressing inhibitory neuron subtype. We observed stronger cross-species conservation of regulatory elements in inhibitory neurons than in excitatory neurons. Single-nucleus methylomes expand the atlas of brain cell types and identify regulatory elements that drive conserved brain cell diversity.
(Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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