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Science. 2017 Aug 11;357(6351):600-604. doi: 10.1126/science.aan3351.

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

Author information

1
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA.
4
Swift Biosciences Inc., 58 Parkland Plaza, Suite 100, Ann Arbor, MI 48103, USA.
5
Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
6
Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
7
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
8
Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu.
9
Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu.
10
Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ecker@salk.edu mbehrens@salk.edu emukamel@ucsd.edu.

Abstract

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.

PMID:
28798132
PMCID:
PMC5570439
DOI:
10.1126/science.aan3351
[Indexed for MEDLINE]
Free PMC Article

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