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

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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.