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

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…

• HH
  Howard Hughes Medical Institute

  Award: award309053
• NI
  National Institute of Mental Health

  Awards: 2T32MH020002, 5U01MH105985, award338010, award338008, award338009, 1R21MH112161
• NH
  National Human Genome Research Institute

  Awards: award309052, 1R21HG009274