期刊
SCIENCE
卷 357, 期 6351, 页码 600-604出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aan3351
关键词
-
资金
- NIH BRAIN initiative grants [5U01MH105985, 1R21MH112161, 1R21HG009274]
- NIH [2T32MH020002]
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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