Epigenetic regulation of human embryonic stem cell differentiation Human embryonic stem cells (ESC) are pluripotent cells derived from embryos at the blastocyst stage of development. Their embryonic origin confers upon them the capacity to proliferate indefinitely in vitro while maintaining their ability to differentiate into a large number of specialised cell types. The use of ESC has great potential for better understanding the early stages of human development and for future biomedical applications, including patient-specific therapies, disease modelling and drug discovery. During embryonic development and ESC differentiation, pluripotent cells with identical genomes give rise to distinct cell types using epigenetic mechanisms to establish lineage-specific transcriptional programmes. Our research group is actively investigating several of these epigenetic mechanisms, ranging from the roles of histone modifying proteins in gene repression, to the coordination and functional output of higher-order chromatin organisation. This PhD project will test the hypothesis that gene regulatory networks are controlled by epigenetic modifications and long-range genome interactions during human ESC differentiation. You will use well-established human ESC differentiation assays, in combination with state-of-the-art genomic and epigenomic approaches, to investigate the dynamics of transcriptional and epigenetic processes. Bioinformatic analyses will identify global and gene-specific changes in gene regulatory networks that may underlie mechanisms controlling stem cell fate decisions. Potential mechanisms will be tested using loss of function approaches with a particular focus on the outcome of ESC differentiation. Results will better define how epigenetic mechanisms underpin lineage-specific transcriptional programs in stem cells and development.
- Rugg-Gunn et al. (2012) Cell-surface proteomics identifies lineage-specific markers of embryo-derived stem cells. Developmental Cell. 22:887.
- Rugg-Gunn et al. (2010) Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo. Proc. Natl. Acad. Sci. USA. 107(24):10783.
- Rugg-Gunn et al. (2005) Epigenetic status of human embryonic stem cells. Nature Genetics. 37(6): 585.