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

造血干细胞（HSCs）是一小群成体干细胞，专门负责所有已知血细胞类型的持续补充。它们存在于骨髓内;这是一个复杂的、异质的环境，已知可以通过介导其最显着的特征直接控制HSC维持组织稳态的能力。一个这样的特征是HSC及其后代的显著迁移能力。例如，已经观察到HSC以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区室进入循环。然而，尽管干细胞成像技术的快速技术进步，干细胞动力学和周围骨髓环境的架构之间的关系的精确性质仍然知之甚少。该项目的一个中心目标是阐明对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，主要是通过对从小鼠骨腔中HSC的活体体内3D成像中提取的数据进行统计分析。然而，该项目的目的是多方面的;从现代生物物理学的角度来看，骨髓细胞成分的固有运动性将造血系统置于被称为“活性物质”的软凝聚态物理学快速发展的领域之下;广义而言，旨在将凝聚态物理学的范式扩展到包括生命系统。HSC固有的自我推进特性和它们必须在其中导航的环境的复杂性提高了发现骨髓室特有的新物理学的可能性。这将通过计算模拟和非平衡统计物理工具的应用相结合来分析集体细胞运动的最小模型来探索。

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.