I joined the lab as a PhD student in June 2013, and have since been thinking about how individual mouse embryonic stem cells (mESCs) make choices following the exit from pluripotency. The lineage choices that such cells make necessarily depend on the signalling stimuli that the cell is exposed to, but is also likely to be contingent on cellular state, including the epigenetic landscape. I am primarily interested in the interplay between these levels of coordination, and how they relate to cellular decision-making.
As an in vitro system, mESCs have enormous potential to provide us with answers to basic developmental biology and embryological questions, including the role of signalling networks on differentiation pathways. Part of my project has been analysing the interplay between Activin/Nodal signalling and Wnt signalling during differentiation to mesendoderm/primitive streak.
I am also particularly interested in cellular state during a differentiation time-course in terms of cellular competence to differentiate. Â Related to this is the question of whether cells exiting the pluripotent state towards a fully committed, differentiated state are indeed free to choose a lineage pathway or whether they are pre-primed for such a decision-point and thereby somewhat poised. Â While this question is likely to have many levels of control, I am focussing particularly on potential epigenetic landscape topology changes.