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 122 for “"HSCs"”.
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Examining the effects of reactive oxygen species on functional potential of HSCS during aging
… play a role in the functional decline of HSCs associated with aging. Measuring DNA damage and ROS levels using the Fragment Length Analysis by Repair Enzyme (FLARE) assay, I show here that there are indeed significantly detectable levels of 8-oxoguanine, a lesion associated with ROS, …
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Identification and Characterization of Distinct Populations of Clonogenic Bone Marrow Stromal Cells Capable of Transferring The Hematopoietic Microenvironment In Vivo and Supporting Lt-Hscs In Vitro
… support long-term multi-lineage reconstituting HSCs, we fractionated BM stromal cells into either the LinNEGPDGFRαβPOSCD105POS and LINNEGPDGFRαβPOSCD105LOW/- populations and tested their capacity to support LT-HSC by co-culturing each population with either 1 or 10 HSCs for 10 days. Following …
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Regulation of Hematopoietic Stem Cells
… the regulation of hematopoietic stem cells (HSCs) that represent rare cells residing in the bone marrow (BM) of adults. They are multipotent cells that have the capacity to differentiate to all mature cells of the blood system and have the capacity to self-renew, i.e. generate new HSCs. These …
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Extrinsic regulation of fate choice in mouse haematopoietic stem cells
… alter fate choice in haematopoietic stem cells (HSCs). For decades cytokines have been used to maintain and expand mouse and human HSCs in vitro, with a number of studies demonstrating that cytokines directly influence HSCs fate choice. In this thesis, I explored the extrinsic regulation of mouse …
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Insulin-Like Growth Factor-Binding Protein 2 Supports Hematopoietic Stem Cell Expansion: From In Vitro to In Vivo
… is often limited by the numbers of HSCs, and robust methods to expand HSCs ex vivo are needed. We previously showed that angiopoietin-like proteins (Angptls), a group of growth factors isolated from a fetal liver HSC supportive cell population, improved ex vivo expansion of HSCs. …
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Mitophagy-Mediated Regulation of ROS Homeostasis During HSC Activation Contributes to Cell Fate
… with low autophagy predicting activation of HSCs, and autophagy deficiency causing the spontaneous loss of quiescence and HSC exhaustion. Although an increase in mitochondrial activity has been suggested as the cause of HSC depletion in autophagy-defective models, the contribution of …
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Single-cell approaches to assess hematopoietic stem cell response to matrix cues
… cells for hematological and immune systems. HSCs reside in the bone marrow within specialized microenvironments known as niches, comprised of various cellular and extracellular components including niche cells, extracellular matrix (ECM), and immobilized or soluble signaling molecules that …
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Molecular Mechanisms in Hematopoietic Stem Cell Aging
… are derived from hematopoietic stem cells (HSCs). In addition, HSCs are able to undergo self-renewing divisions whereby new HSCs are produced. This is an extremely important feature of HSCs in order to ensure the existence of the HSC pool that is paramount to provide life-long hematopoiesis. …
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Investigation of a suppression of asymmetric cell kinetics (SACK) approach for ex vivo expansion of human hematopoietic stem cells
Ex vivo expansion of hematopoietic stem cells (HSCs) is a long-standing challenge faced by both researchers and clinicians. To date, no robust, efficient method for the pure, ex vivo expansion of human HSCs has been demonstrated. Previous methods primarily induced the expansion of committed …
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Refining Our Understanding of the Hematopoietic Stem Cell Niche
… studying blood-forming hematopoietic stem cells (HSCs) is to understand the mechanisms by which HSCs are maintained in the bone marrow, so that they can be grown outside of the body and used in lieu of or in combination with bone marrow transplantation to treat hematopoietic illnesses. HSCs, as …
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PTEN regulates the BMI1-mediated self-renewal of long-term hematopoietic stem cells in developmental and stress conditions
… long-term hematopoietic stem cells (LT-HSCs) maintain stem cell pools and differentiate into hematopoietic progeny. In addition to its critical role in the daily production of blood cells, LT-HSCs are able to resist the threats posed by various types of stress. However, our understanding …
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Role of S6K1 in regulating self-renewal of hematopoietic stem cells and propagatoin of leukemia
… and function of hematopoietic stem cells (HSCs) is regulated by numerous signaling pathways including Akt-mechanistic target of rapamycin complex1 (mTORC1) pathway. Dysregulation of this pathway results in impaired HSC function and contributes to the development of hematologic malignancies. …
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MOLECULAR CHARACTERISATION OF EXPANDED MOUSE HAEMATOPOIETIC STEM CELLS USING A NOVEL IN VITRO REPORTER STRATEGY
Haematopoietic stem cells (HSCs) are responsible for the lifelong maintenance of the blood forming system which produces trillions of blood cells daily. They are able to achieve this because of two defining properties: 1) they can give rise to progeny which eventually form all of the blood cell …
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Discovery of Peptide and Aptamer Ligands for Targeted Drug Delivery to Hepatic Stellate Cells
… approaches to identify Hepatic Stellate Cells (HSCs) targeting ligands using phage-display library biopanning and systematic evolution of ligands by exponential enrichment (SELEX). These HSC-specific ligands can be used for diagnosis and therapy of liver fibrosis. The mechanism of fibrogenesis …
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Identification of Novel Regulators in Hematopoiesis: Roles for Gfer in Hematopoietic Stem Cell Proliferation and CaMKK2 in the Restriction of Granulopoiesis
… is of critical importance as dysregulation of HSCs can lead to hematopoietic deficiencies or malignancies such as leukemogenesis. While the signaling mechanisms that regulate HSC homeostasis and function are not well understood, our previous studies have identified a calcium/calmodulin …
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Single-cell approaches reveal functional and molecular heterogeneity in malignant haematopoietic stem cells
… disease in mouse haematopoietic stem cells (HSCs), using JAK2 V617F mutant myeloproliferative neoplasms (MPNs) as a model. This study utilises single-cell gene expression and functional assays to identify a subset of JAK2 V617F mutant HSCs that display defective self-renewal. This defect is …
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Protein Tyrosine Phosphatase Receptor Type S (PTPRS) Regulates Hematopoietic Stem Cell Self-Renewal
… of PTPs in counterbalancing PTK signaling in HSCs however remain incompletely understood. Our laboratory has demonstrated that a heparin binding growth factor, Pleiotrophin (PTN), promotes the expansion of murine long-term (LT)-HSCs via binding to a PTP, protein tyrosine phosphatase receptor …
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Identification of Unique Hematopoietic Stem Cell Properties
… of all blood cell lineages. Steady state HSCs are largely quiescent and we demonstrate that the kinetics of HSC cell cycling are slower compared to more committed progenitor cells also during expansion and self-renewal ex vivo and in physiological conditions. Such slow kinetics during cell …
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Unfolded Protein Response (UPR) Signaling in Hepatic Stellate Cells (HSC) as a Key Regulator of Liver Fibrosis
… is the activation of hepatic stellate cells (HSCs), which secrete extracellular matrix (ECM) proteins such as collagen to form fibrotic scars. Activated HSCs produce vast amounts of fibrotic proteins that require folding and processing prior to secretion. Increased protein folding demands …
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Deciphering ARAP3 Functions in Hematopoiesis and Hematopoietic Stem Cells
… in hematopoiesis and hematopoietic stem cells (HSCs). In this thesis, we aim to elucidate the potential cell-autonomous and non-cell-autonomous roles of ARAP3 in hematopoiesis and HSCs using several conditional knockout (CKO) transgenic mouse models in addition to the KI/KI mutant mouse model. …
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