The Physics of Stem Cell Dynamics and Localisation in the Bone Marrow Environment

骨髓环境中干细胞动力学和定位的物理学

• 批准号: 1814640
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1814640
• 关键词: Physics; Stem; Cell; Dynamics; Localisation

Haematopoietic stem cells (HSCs) are a small population of adult stem cells solely responsible for the continuous replenishment of all known blood cell types. They reside within the bone marrow; a complex, heterogeneous environment which is known to directly control the HSCs ability to maintain tissue homeostasis through mediating their most salient features. One such feature is the remarkable migratory capacity of HSCs and their progeny. For example, it has been observed that HSCs periodically leave the bone marrow compartment to enter circulation in a manner which is thought to be correlated with the mammalian circadian rhythm. However, despite rapid technological advances in stem cell imaging techniques, the precise nature of the relationship between stem cell dynamics and the architecture of the surrounding bone marrow environment remains poorly understood. One central aim of this project is to elucidate a quantitative understanding of the dynamical behaviour of HSCs and their corresponding interactions with the bone marrow micro-environment, primarily through the statistical analysis of data extracted from the live in vivo 3D imaging of HSCs in murine bone cavities. However, the purpose of this project is multifaceted; as from the viewpoint of modern biological physics the inherent motility of the cellular constituents of the bone marrow places the haematopoietic system under the remit of a rapidly advancing area of soft-condensed matter physics known as 'Active Matter'; which broadly speaking, aims to extend the paradigm of condensed matter physics to include living systems. The intrinsic self-propelled property of HSCs and the complex nature of the environment in which they must navigate themselves through raises the possibility of uncovering novel physics unique to the bone marrow compartment. This will be explored through a combination of computational simulation and an application of the tools of non-equilibrium statistical physics to analyse minimal models of collective cellular motion.

造血干细胞（hsc）是一小部分成体干细胞，完全负责所有已知血细胞类型的持续补充。它们存在于骨髓中；一个复杂的，异构的环境，已知直接控制hsc维持组织稳态的能力，通过介导其最显著的特征。其中一个特点是造血干细胞及其后代具有显著的迁移能力。例如，已经观察到造血干细胞以一种被认为与哺乳动物昼夜节律相关的方式周期性地离开骨髓腔室进入循环。然而，尽管干细胞成像技术快速发展，干细胞动力学和周围骨髓环境结构之间关系的确切性质仍然知之甚少。该项目的一个中心目标是阐明hsc的动态行为及其与骨髓微环境的相应相互作用的定量理解，主要是通过对小鼠骨腔中hsc的活体3D成像提取的数据进行统计分析。然而，这个项目的目的是多方面的；从现代生物物理学的观点来看，骨髓细胞成分的固有运动性将造血系统置于软凝聚态物理快速发展的领域——“活性物质”的研究范围之内；从广义上讲，旨在将凝聚态物理的范例扩展到包括生命系统。造血干细胞固有的自我推进特性和它们必须在其中导航的复杂环境的性质，提高了发现骨髓腔室独特的新物理学的可能性。这将通过结合计算模拟和应用非平衡统计物理工具来分析集体细胞运动的最小模型来探索。