MIG Seminar Series - Heather Lee - Single Cell Epigenomics for Analysis of Rare and Heterogeneous Cell Populations
“Single Cell Epigenomics for Analysis of Rare and Heterogeneous Cell Populations”
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 (1). 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) (2), which provides quantitative, single-nucleotide information on DNA methylation for up to 50% of cytosines across the genome. Extending on this work, we reported parallel single-cell methylome and transcriptome sequencing (scM&T-seq) (3), 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. Ongoing technological developments will also be described. 1. Clark, Lee, Smallwood et al. (2016) Genome Biol 17:72. 2. Smallwood, Lee, et al. (2014) Nat Methods 11:817-20. 3. Angermueller, Clark, Lee, Macaulay, et al. (2016) Nat Methods 13:229-32.
Dr Heather Lee, Cancer Institute NSW EC Fellow
Dr Heather Lee
Cancer Institute NSW EC Fellow
Hunter Medical Research Institute & Newcastle University
Heather completed her PhD at the Garvan Institute of Medical Research where she investigated hormonal control of mammary gland development and breast cancer. Her research focused on the transcription factor, Elf5, which plays key roles in breast development during pregnancy and acquisition of antioestrogen resistance in breast cancer. After discovering lineagespecific DNA methylation of the Elf5 promoter in the mammary epithelium, Heather decided to undertake postdoctoral research in the field of epigenetics. In 2012, Heather relocated to Cambridge, UK, where she joined the laboratory of Professor Wolf Reik. Using mouse embryonic stem cells as an experimental model, Heather revealed unprecedented dynamic heterogeneity in DNA methylation. Heather also developed groundbreaking singlecell sequencing technologies for the parallel analysis of genomewide DNA methylation and gene expression in the same single cell. Heather joined the University of Newcastle in February 2017, where she leads a research group at the Hunter Medical Research Institute. Her current research focuses on epigenetic heterogeneity in acute myeloid leukaemia.