Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 56 for “"haematopoiesis"”.
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The natural history of clonal haematopoiesis
… healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other diseases, we have limited understanding of its natural history and how this relates to clinical phenotype. Objectives 1. To characterise the behaviour of CH across the human …
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The role of GATA-1 isoforms in haematopoiesis
… and physiological role of GATA-1s in haematopoiesis. Some insight has been gained into the pathological role of GATA-1s by creation of a GATA-1s knock-in transgenic mouse and by experiments looking at the ability of GATA-1s to rescue GATA-1 deficient embryonic stem (ES) cell lines. …
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Clonal dynamics of haematopoiesis across the human lifespan
… or blood loss; and increased risk of clonal haematopoiesis and blood cancers. The cellular alterations that underpin these age-related phenotypes, which typically manifest in individuals aged over 70, remain elusive. In my thesis I have aimed to investigate whether changes in HSC population …
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Modelling the age-dependent dynamics of clonal haematopoiesis
… stem cells, this process, known as clonal haematopoiesis (CH), can often be detected years before the onset of haematological cancer, raising the possibility that individual cancer risk could be inferred from a routine blood sample. While recent studies have begun to quantify CH dynamics -- …
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Charting the single-cell transcriptional landscape of haematopoiesis
High turnover in the haematopoietic system is sustained by stem and progenitor cells, which divide and mature to produce the range of cell types present in the blood. This complex system has long served as a model of differentiation in adult stem cell systems and its study has important clinical …
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Single cell -omic landscapes in normal and perturbed haematopoiesis
… extending to millions of cells. In the field of haematopoiesis, much of our knowledge is derived from the study of model organisms, of which the most commonly used is the mouse. Unbiased single cell datasets of murine haematopoietic stem and progenitor cells have proved invaluable to drive new …
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Using single cell transcriptomics to characterise endothelial populations in embryonic haematopoiesis
… potential new regulators of embryonic haematopoiesis and characterising the endothelial precursors as quiescent in nature. Furthermore, ex vivo and in vitro culturing of CD44+ cells identified a functional role for CD44 in the process of EHT. The precise mechanism by which CD44 and its …
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Single-cell Protein-Transcriptome Atlas of Haematopoiesis across the Human Lifespan
… diseases. Throughout an individual's life, human haematopoiesis demonstrates significant variations, likely in response to changing demands and physiological needs. Moreover, age-related alterations in the blood system are believed to impede its functionality. Both transcriptomic and proteomic …
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Understanding the role of extrinsic regulators in normal and malignant haematopoiesis
… regulators play in both normal and malignant haematopoiesis. Recent evidence suggests that variations in key molecules can directly modulate haematopoietic stem cell (HSC) fate, implicating noncell intrinsic mechanisms for both maintaining homeostasis and for driving disease development. This …
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Modelling Embryonic Haematopoiesis Using In Vitro State-of-art Gastruloid Culture
… to produce HSPCs from mouse ES cells and model haematopoiesis which occurs at the aorta-gonad-mesonephros (AGM) region of the mouse embryo. In this project, the gastruloid culture protocol is modified to maintain a gastruloid (gastrulation organoid) for up to 216 hr by introducing a 2iLIF …
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Deciphering the Mechanisms of Heterogeneity within Haematopoiesis in Health, Development & Disease
Haematopoiesis represents one of the most intricate stem cell processes; in terms of the range of diverse cellular output and the extent of turnover through the system. It also stands as one of the most well characterised cellular systems given the accessibility of the tissue. As our understanding …
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Responses to Tumour initiating factors and Regulation of Normal and Malignant Haematopoiesis
The haematopoietic stem cell (HSC) resides within a specific environment enabling it to retain its self-renewal capacity or quiescent state. It is proposed that the HSC niche is hypoxic, a milieu within which the HSC is protected from intrinsic and extrinsic stimuli. We have investigated the …
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The role of the Dnmt3aR882H mutation in the evolution of clonal haematopoiesis.
… mutations are very frequent events in clonal haematopoiesis of indeter- minate potential (CHIP), and considered one of the earliest genetic events during the development of haematopoietic malignancies. Individuals with CHIP, in spite of having a normal full blood count are at increased risk of …
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Mechanisms driving the expansion and progression of splicing factor-mutant clonal haematopoiesis
Clonal haematopoiesis (CH) describes the expansion of haematopoietic stem cells (HSCs) and their progeny due to the acquisition of somatic mutations. CH can be detected almost ubiquitously with advancing age and is associated with an increased risk of incident haematological malignancy and several …
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An investigation of the role of TRIB2 in steady state and stressed haematopoiesis
… pseudokinases (TRIB1-3). Here, we studied murine haematopoiesis after Trib2 ablation under steady state and proliferative stress conditions, including genotoxic and oncogenic stress. At the steady state, we found that TRIB2 loss did not adversely affect peripheral blood cell counts and …
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Trees and Forests: Data Science and Machine Learning Approaches to Characterise Clonal Haematopoiesis
Clonal haematopoiesis (CH), the expansion of a haematopoietic stem cell (HSC) driven by somatic mutations in leukaemia-associated genes, is a common age-related phenomenon that affects more than 20% of adults aged over 70 years. As the shared precursor of most myeloid neoplasms (MN), timely …
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Synthesising executable gene regulatory networks in haematopoiesis from single-cell gene expression data
A fundamental challenge in biology is to understand the complex gene regulatory networks which control tissue development in the mammalian embryo, and maintain homoeostasis in the adult. The cell fate decisions underlying these processes are ultimately made at the level of individual cells. Recent …
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The evolutionary dynamics of clonal haematopoiesis and its progression to acute myeloid leukaemia
… healthy individuals, a phenomenon termed ‘clonal haematopoiesis’. However, most individuals with clonal haematopoiesis will never progress to AML and so a key challenge is the identification of individuals most at risk. To do this, we need a better understanding of the evolutionary dynamics of …
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Novel roles of KAT2A chromatin complexes ATAC and SAGA in normal and malignant haematopoiesis
Haematopoiesis is a dynamic process by which the full array of blood cell types originates from multipotent haematopoietic stem cells (HSCs). The blood system has long been an attractive model to explore how cell fate decisions are conducted at the molecular level, to generate the vast diversity of …
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Clonal haematopoiesis of indeterminate potential and the role of inflammation in its association with atherosclerosis
… inflammation in ageing remains unclear. Clonal haematopoiesis of indeterminate potential (CHIP) is a common age-associated condition in which haematopoietic stem cells acquire somatic mutations, leading to clonal expansion and aberrant cellular functions. CHIP has been suggested to drive CVD via …
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