Defining the Role of NF-kB During Embryonic Stem Cell Differentiation

The Nuclear Factor-kappaB (NF-kB) pathway is a dynamic signalling network that has been long studied for its role in inflammation, immunity, and oncogenesis in the adult organism. The inherent complexity of NF-kB signalling provides a high degree of flexibility in mediating a precise transcriptional response to a heterogenous signalling environment. This complexity is seen in the diversity of NF-kB transcription factors and inhibitory proteins, the combination of which can yield distinct transcriptional responses, and also in its dynamic feedback mechanisms whereby sustained stimulation of NF-kB signalling can result in oscillations of transcriptional output. While it's role in inflammation and oncogenesis in adult tissues continues to be an area of intense study, the NF-kB network has only recently been implicated in moderating cell fate decisions during early development and requires further investigation.
We aim to characterise what function the NF-kB pathway has in mediating both the maintenance and exit of mouse embryonic stem cells from pluripotency. By coupling bulk cell techniques with single cell analyses we will define the role of NF-kB signalling during these cell fate transitions and determine whether the dynamics of specific NF-kB proteins can influence the route of differentiation. This integration of NF-kB signalling into the network of known mechanisms that regulate the cellular exit from pluripotency will help us to better understand, and ultimately better control, the process of differentiation for future application.