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

核因子- κ b （NF-kB）通路是一个动态信号网络，长期以来一直被研究其在成人机体炎症、免疫和肿瘤发生中的作用。NF-kB信号的固有复杂性为介导对异质信号环境的精确转录反应提供了高度的灵活性。这种复杂性体现在NF-kB转录因子和抑制蛋白的多样性中，它们的组合可以产生不同的转录反应，也体现在其动态反馈机制中，即持续刺激NF-kB信号传导可以导致转录输出的振荡。虽然NF-kB网络在成人组织炎症和肿瘤发生中的作用仍然是一个深入研究的领域，但直到最近才发现NF-kB网络在早期发育过程中与调节细胞命运决定有关，需要进一步研究。我们的目标是描述NF-kB通路在介导小鼠胚胎干细胞多能性的维持和退出中的功能。通过将大细胞技术与单细胞分析相结合，我们将确定NF-kB信号在这些细胞命运转变中的作用，并确定特定NF-kB蛋白的动态是否会影响分化途径。将NF-kB信号整合到调节细胞多能性退出的已知机制网络中，将有助于我们更好地理解并最终更好地控制分化过程，以用于未来的应用。

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.