The aim of my research is to understand the early lineage decisions of embryonic stem (ES) cells. I am interested in how local communication between individual cells influences these decisions. A related interest is to understand why seemingly homogenous populations of ES cells differentiate at different rates, or into different lineages, even under simple, fully defined differentiation protocols.
We aim to understand how cells steer a path from pluripotency towards lineage commitment, and in particular to understand why differentiation response can be variable between individual cells.
We have used a series of Yeast-two-Hybrid screens to identify pro-differentiation bHLH transcription factors that are expressed in ES cells but held in an inactive state through the action of Id proteins. One transcription factor that emerged from this screen marks an epiblast-primed subpopulation of ES cells, and can drive maturation towards differentiation-primed epiblast once released from inhibition of Id.
In parallel, we have found that Id influences the adhesive properties of ES cells. This has led us to explore how changes in cell adhesion are coupled with changes in cell identity during the exit from pluripotency.
Both of these strands of our work converge to help explain how pluripotent cells become receptive to differentiation cues.