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

定义 NF-kB 在胚胎干细胞分化过程中的作用

• 批准号: 2599454
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2599454
• 关键词: Defining; Role; NF; kB; During

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.

核因子-kB（NF-kB）通路是一种动态信号网络，其在成年生物体中的炎症、免疫和肿瘤发生中的作用已被长期研究。NF-kB信号传导的固有复杂性在介导对异源信号传导环境的精确转录应答方面提供了高度的灵活性。这种复杂性可见于NF-κ B转录因子和抑制蛋白的多样性，它们的组合可以产生不同的转录反应，并且还可见于其动态反馈机制，其中NF-κ B信号传导的持续刺激可以导致转录输出的振荡。虽然它在成人组织中的炎症和肿瘤发生中的作用仍然是一个深入研究的领域，但NF-kB网络最近才被发现在早期发育过程中参与调节细胞命运决定，需要进一步研究。我们的目的是阐明NF-κ B通路在介导小鼠胚胎干细胞多能性的维持和退出中的作用。通过将大量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过程中的作用，并确定特定NF-kB蛋白的动态是否会影响分化途径。将NF-kB信号传导整合到调节细胞退出多能性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，以供未来应用。