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 24 for “"Megakaryocyte"”.
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Platelet Dense Granules Mature Within Late Stages Of Megakaryocyte Differentiation By Cargo Delivery
… of the platelet precursor cell, the megakaryocyte (MK). DGs are thought to fully mature within MKs prior to platelet formation. Here I challenge this notion by exploiting vital fluorescent dyes to distinguish mildly acidic DGs from highly acidic compartments in platelets and MKs. In …
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Novel insights into megakaryopoiesis, thrombopoiesis and acute coronary thrombosis: transcriptome profiling of the haematopoietic stem cell, megakaryocyte and platelet
… of human haematopoietic stem cells (HSCs), megakaryocytes and platelets to gain insights into steady state and accelerated thrombopoiesis that occurs in states of haemostatic demand and in thrombosis by applying these findings to the pathological setting of acute coronary thrombosis. To …
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New molecular and cellular aspects of mutant calreticulin in Myeloproliferative Neoplasms
… neoplasms (MPNs) characterised by megakaryocyte hyperplasia. Despite the large body of research built around CALR mutations, many aspects of the oncogenic mechanisms of CALR in MPNs remain unanswered. This investigation aims to investigate whether CALR mutations affect the nature of …
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Forward programming of human pluripotent stem cells to a megakaryocyte-erythrocyte bi-potent progenitor population: an in vitro system for the production of platelets and red blood cells for transfusion medicine.
… factors (TFs), pushing iPSCs towards the megakaryocyte lineage, to produce mature megakaryocytes, the platelet precursor cell type. A major limitation of the forward programming technique is a reliance of lentiviral transduction to overexpress the three TFs, which leads to a number of …
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Characterization of human myeloid progenitors and their differentiation
… to the neutrophil/monocyte and erythrocyte/megakaryocyte lineages. The objective of this thesis was to further characterize early human myeloid development. As a first step we established a map over neutrophil and erythroid differentiation-associated changes both on the surface and in gene …
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The Role of Meis1 in Hematopoietic Development
… involved the fate choice between erythroid and megakaryocyte lineages. First, we found that endogenous <italic>Mesp1</italic> indirectly induces <italic>Meis1</italic> and <italic>Meis2</italic> in endothelial cells derived from embryonic stem: ES) cells. Overexpression of <italic>Meis1</italic> …
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Development and assessment of supercharged platelets as a novel drug delivery mechanism for promoting cardiac regeneration
… was employed for the genetic engineering of megakaryocytes, the precursor cells of platelets. Lentiviral plasmids, designed for the targeted delivery of proteins to the megakaryocyte and platelet α-granules, were modified to incorporate FGF2, VEGFA and TB4. Subsequently generated lentivirus …
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Mapping the transcriptional landscape of haematopoietic stem and progenitor cells
… recapitulated differentiation of HSCs towards megakaryocyte–erythrocyte progenitors and lymphoid-primed multipotent progenitors. By comparing these two models, a rule specific to the megakaryocyte-erythrocyte progenitor network was identified, in which GATA2 positively regulated Nfe2 and …
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Regulation of Myeloid Leukemia Cells by Platelet Factor 4
… Here, we examined the efficacy of the megakaryocyte-derived chemokine platelet factor 4 (PF4) to inhibit LSC proliferation and alter the course of AML disease progression in syngeneic mouse models and human AML cells. We found that PF4 preferentially acts on LSCs via low-density …
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Evaluation of the actin architecture in dysplastic megakaryocytes expressing the NUP98-HOXD13 leukemic fusion gene
… with macrothrombocytopenia due to impaired megakaryocyte (MK) differentiation. Transgenic mice that express the NUP98-HOXD13 (NHD13) fusion gene is a model for MDS and recapitulates the key features of MDS. The study investigated the hypothesis that expression of NHD13 disrupts actin …
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Neuronal regulation of haematopoietic stem cell ageing and age-related blood disorders through the microenvironment
… ageing. Whereas β2-AR promotes myeloid and megakaryocyte (Mk) differentiation through stromal-cell-derived interleukin-6 (IL-6), reduced β3-AR signalling accelerates ageing by remodelling HSC niches and diminishing lymphoid-biased HSCs. Similarly, non-HSC-autonomous premature haematopoietic …
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Intercellular Feedback in Hematopoiesis
… cell self-renewal is regulated by a balance of megakaryocyte-derived stimulatory factors vs. monocyte-derived inhibitory factors. To understand how the experimentally identified positive and negative regulatory signals are integrated at the intra-cellular level, we define a literature-derived …
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Infusing Factor Viii-Expressing Platelets Or Megakaryocytes As A Novel Therapeutic Strategy For Hemophilia A
… patients is ectopically expressing FVIII in megakaryocytes and platelets. This FVIII, termed pFVIII, is stored in alpha granules of platelets and is capable of restoring hemostasis in FVIIInull mice, even in the presence of circulating inhibitors. pFVIII has been proposed to be used for gene …
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Integrin α2 and Akt in early hematopoiesis
… in the immature CD34+CD38-CD45RA- bipotential megakaryocyte-erythrocyte progenitors in human bone marrow, providing a means for enriching this novel bipotent progenitor population for further studies on early megakaryocytic and erythroid lineage fate decisions. In addition, we demonstrated that …
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Hematopoietic Stem Cells and Progenitors in Murine Autoimmune Arthritis
… cell related transcripts at the expense of megakaryocyte and erythroid transcripts. In vitro, KSL cells from arthritic mice were markedly superior in generating myeloid cells, including osteoclasts. When KSL cells from arthritic and control mice were competitively transplanted arthritic KSL …
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Cytokine Regulation of Hematopoietic Stem Cells and Lymphopoiesis
… and lymphocyte potential, but little or no megakaryocyte and erythroid potential, we provide evidence for a strict separation of myelopoiesis and lymphopoiesis, not being the first lineage commitment step of HSCs.
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Functional and Transcriptional Heterogeneity of the Human Haematopoietic Stem Cell Pool at Steady-State and Under Inflammation
… most lineage types were produced: My, Ly, Ery, megakaryocyte (Meg) and mast cells (MC). Studying the differentiation trajectories observed in this model, I identified IL1RL1, the gene encoding the IL-33 receptor, ST2, as a potential modulator of the Ery, Meg and MC branch. When exposed to IL-33, …
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Charting the single-cell transcriptional landscape of haematopoiesis
… Gata2 that was unique to differentiation towards megakaryocyte-erythroid progenitors, which was subsequently experimentally validated. The next study focused on investigating the link between transcriptional and functional heterogeneity within blood progenitor populations. Single-cell profiles of …
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An investigation of the role of ACTN1 in platelet formation and of platelet function in myeloma
… actinin-1 in platelet production were explored. Megakaryocyte maturation in terms of polyploidy was assessed in CMK and MEG-01 cell lines expressing mutant actinin-1 but no significant disruption was noted. Primary murine megakaryocytes were used to image WT actinin-1 and actinin-4 in two key …
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The Role of Platelets In Ovarian Carcinoma
… 50%. Complete blood counts and number of mature megakaryocytes in the spleen and bone marrow were compared between control mice and ovarian cancer-bearing mice. Plasma levels of key megakaryo- and thrombopoietic factors including thrombopoietin (TPO), IL-1a, IL-3, IL-4, IL-6, IL-11, G-CSF, …
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