The epigenome is an ensemble of chemical modifications of DNA and chromatin. Genome-wide mapping of epigenomic signatures is one of the most effective approaches for identifying gene regulatory elements such as enhancers. Our recent study demonstrated robust classification of brain cell types using single-cell DNA methylation profiles. Single-cell epigenomic approaches enable unbiased mapping of the regulatory landscape for virtually all brain cell populations. As part of the BRAIN Initiative Cell Census Network (BICCN), we are analyzing cell type and gene regulation diversity of the entire mouse brain with fine spatial resolution. Single-cell DNA methylome profiles are being produced from 116 dissected brain regions. To date we have generated over 46,000 single-cell methylomes from over 23 brain regions. We uncovered pervasive DNA methylation differences between excitatory neurons located in distinct cortical regions, whereas inhibitory neurons show less regional specification in the cortex. We are further applying our single-cell DNA methylation assay to study the cell type diversity of human frontal cortex. DNA methylation signatures allow robust classification of both neuronal and glial cell sub-types, and prediction of regulatory sequences for human cortical cell populations. We identified enrichment of genetic variants associated with brain diseases such as schizophrenia in subtypes of excitatory and glial cells. Our single-cell epigenomic strategy provides opportunities to determine cell-type specific contributions of non-coding sequences in brain diseases.
Chongyuan Luo received his bachelor’s degree from China Agricultural University, Beijing, China. During his Ph.D., he studied histone modifications of the model plant species Arabidopsis thaliana using high-throughput sequencing approaches. During his postdoc training in Joe Ecker’s lab at Salk Institute, he developed experimental and computational methods to analyze the epigenome of mammalian brains at cell-type and single cell levels. The goal of Luo’s research is to define the genetic and epigenetic basis of brain diseases, with a particular
Chongyuan Luo, Ph.D.
Salk Institute for Biological Studies
12:00 pm at Van Andel Institute
Conference Room 3104/3105
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