Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex
Methylation and the single neuronal cell
The presence or absence of methylation on chromosomal DNA can drive or repress gene expression. Now, a comprehensive map of methylation variation in neuronal cell populations, including a between-species comparison, illustrates how epigenetic diversity plays important roles in neuronal development. Luo et al. examined how DNA methylation is both similar and different within neurons at the single-nucleus level in humans and mice. They identified 16 mouse and 21 human neuronal clusters, with greater complexity of excitatory neurons in deep brain layers than in superficial layers.
Science, this issue p. 600
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.
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Supplementary Material
Summary
Materials and Methods
Supplementary Text
Figs. S1 to S17
Tables S1 to S9
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Information & Authors
Information
Published In
Science
Volume 357 • Issue 6351 • 11 August 2017
Pages: 600 - 604
History
Received: 31 March 2017
Accepted: 13 July 2017
Copyright
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
This is an article distributed under the terms of the Science Journals Default License.
Authors
Funding Information
http://dx.doi.org/10.13039/100000011Howard Hughes Medical Institute: award309053
http://dx.doi.org/10.13039/100000025National Institute of Mental Health: award338008, 5U01MH105985
http://dx.doi.org/10.13039/100000025National Institute of Mental Health: award338009, 1R21MH112161
http://dx.doi.org/10.13039/100000025National Institute of Mental Health: award338010, 2T32MH020002
http://dx.doi.org/10.13039/100000051National Human Genome Research Institute: award309052, 1R21HG009274
