Single-cell epigenomics for analysis of heterogeneous and rare cell populations

Lee HJ

The University of Newcastle.

Single-cell sequencing technologies are revolutionising our understanding of heterogeneous cell populations in development and disease. Incorporation of epigenetic information with single-cell transcriptomic and genomic analyses will provide valuable insights into the molecular mechanisms of gene regulation (Clark, Lee, Smallwood et al. 2016 Genome Biol 17:72). DNA methylation occurs on cytosine residues of CpG dinucleotides in mammalian cells. This epigenetic modification is dynamically regulated during development and is globally dysregulated in many cancer types. We developed single-cell bisulphite sequencing (scBS-seq) (Smallwood, Lee, et al. 2014 Nat Methods 11:817-202), which provides quantitative, single-nucleotide information on DNA methylation for up to 50% of cytosines across the genome. Extending on this work, we recently reported parallel single-cell methylome and transcriptome sequencing (scM&T-seq) (Angermueller, Clark, Lee, Macaulay, et al. 2016 Nat Methods 13:229-32), which allows both DNA methylation and gene expression to be assayed from the same single cell. To illustrate the power of integrated single-cell multi-omics, biological insights gained from scM&T-seq analysis of mouse embryonic stem cells will be presented.