The allocation of cells to a specific lineage is directed by the activities of key signalling pathways and developmentally regulated transcription factors that in turn regulate gene expression. Modulating these factors can maintain the pluripotency or direct the differentiation of stem cells.
We have generated inducible mouse embryonic stem (mES) cell lines that overexpress various transcription factors and seek to identify the molecular hierarchy involved in disruption of the pluripotency regulatory network and induction of differentiation.
We aim to characterise the genetic and epigenetic mechanisms involved in pluripotency inhibition and investigate the impact of stem cell state and signalling on lineage decisions. Understanding the basis of lineage restriction will further elucidate events in early embryogenesis and facilitate efforts to direct stem cell differentiation for disease modelling and therapeutic application.