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 39 for “"Human induced pluripotent stem cell"”.
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Human induced pluripotent stem cell models of Rett Syndrome reveal deficits in early cortical development
… the course of neurogenesis in MeCP2-deficient human neurons with the use of induced pluripotent stem cells (iPSCs) derived from RTT patient skin samples. We generated a variety of monolayer and 3D neuronal models and found that RTT phenotypes are present at the earliest stages of brain …
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Modeling the Effects of Mechanical Loading on Hypertrophic Cardiomyopathy Pathogenesis in Human Induced Pluripotent Stem Cell derived Micro Heart Muscle
… Promising approaches in tissue engineering and stem cell biology have significantly improved the structural and functional maturity of the engineered heart tissue derived from human induced pluripotent stem cells, which can be served as a complementary method to traditional mouse models. …
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Contractile Properties of Striated Muscle in Development and In Disease
… development and disease at the protein, subcellular, and cellular level. Distal arthrogryposis is a skeletal muscle birth defect that can be caused by a mutation in embryonic myosin; herein, I have found that the continued muscle dysfunction is linked to a delay in relaxation, likely from …
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Modeling Alzheimer's Disease Using CRISPR/CAS9 Gene Editing and Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms
… A probable source of this lack of understanding stems from the poor disease model systems that have been utilized in the field for many years. Recently, advances in human induced pluripotent stem cell (iPSC) technology has enabled the study of uniquely human diseases, such as AD, in human tissue. …
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The Functional Role for Chromatin Loops in Gene Expression Control During Human Neuron Maturation
… CTCF occupancy, and mRNA levels in post-mitotic human neurons remains an open question. Here, we summarize the field of epigenetics and chromatin in neuroscience, examine neural model systems, and build an auxin-inducible degron to deplete the architectural protein CTCF and disrupt loops …
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Effects of the MYH7 R369Q Dilated Cardiomyopathy-causing Mutation on Myosin Crossbridge Kinetics and Cardiomyocyte Contractility
… of this mutation on the contractile system within a cardiomyocyte that results in hypocontractility. To better understand the biochemical and biophysical effects of R369Q mutation, this study utilized CRISPR/Cas9-edited R369Q homozygous human induced pluripotent stem cell-derived …
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Stretch Injury Alters Calcium Dynamics and Actin Organization in Human Astrocytes
… pathology. This thesis investigates how human induced pluripotent stem cell (hiPSC)- derived astrocytes respond to mechanical strain, aiming to reproduce changes in astrocyte behavior that can initiate neurodegeneration. In this research, a two- dimensional in vitro stretch model was used …
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Development of collagen-based scaffolds for differentiation of induced pluripotent stem cells
… engineering. A collagen hydrogel can provide cells with a porous and soft environment to proliferate and differentiate. However, lacking mechanical stiffness and shrinkage resistance made it a challenge to sustain shape and size during a long stem cell differentiation process. In addition, a …
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Using single-cell RNA-seq to assess the effect of common genetic variants on gene expression during development
… to measure gene expression at the single cell level, and the chance to study cellular heterogeneity. This represents a remarkable advance over traditional bulk sequencing methods, particularly to study cell fate commitment events in development. The challenge of studying early human …
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Gatekeeper Connexin43 Phosphorylation Events Regulate Cardiac Gap Junction Coupling During Stress
… cardiomyocytes, effecting not only direct intercellular electrical coupling, but the localization of other junctional structures and ion channels. Alterations in Cx43 expression occur in essentially all forms of heart disease and is therefore a topic of intense study. Posttranslational …
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Statistical analysis of neuronal data: Development of quantitative frameworks and application to microelectrode array analysis and cell type classification
… analyse bursting activity in novel recordings of human induced pluripotent stem cell-derived neuronal networks. Results from this review of burst analysis methods are then used to inform the development of a framework for characterising the activity of neuronal networks recorded on MEAs, using …
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Investigating the Biomechanical and Electrophysiological Responses of Astrocytes to Mechanical Trauma
… the brain’s primary homeostatic glial cells, respond dynamically to injury, and alterations in their calcium signaling have been implicated in both TBI and AD pathology. Human induced pluripotent stem cell (hiPSC)-derived astrocytes cultured in 2D monolayers can be mechanically …
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Localizing Strain in a 2D in vitro Stretch System to Model Regional Injury Dynamics
… coexisting populations of injured and uninjured cells. The previously established system uses a flexible polydimethylsiloxane (PDMS) membrane indented by a rigid post to deliver a controllable, clinically relevant stretch to 2D cultures. To induce strain heterogeneity, the system was modified to …
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Engineered Heart Tissues for Advanced Disease Modeling
Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful, in vitro tool for investigating cardiac pathologies. Although hiPSC-CMs have a relatively immature phenotype compared to primary adult cardiomyocytes, their physiological relevance can be improved by …
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Engineering human hepatic tissue for modeling liver-stage malaria
… liver stage has been difficult due to a lack of human liver models that robustly recapitulate host-pathogen interactions in a physiologically relevant cell type. Through the application of hepatic tissue engineering concepts and techniques, this thesis sought to develop advanced models of …
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IN VIVO AND IN VITRO EVALUATION OF THE COMBINATION OF RNA INTERFERING AND GENE THERAPY FOR TREATING MITOFUSIN2-RELATED DISEASES
… essential for mitochondrial networking in most cells. Autosomal dominant mutations in the MFN2 gene cause Charcot-Marie-Tooth type 2A disease (CMT2A), a severe and disabling sensory-motor neuropathy. Here, we propose a novel therapeutic strategy tailored to the correction of the root genetic …
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MODELING AND MODULATING MYELOID CELL-MEDIATED NEUROINFLAMMATION FOLLOWING HUMAN IMMUNODEFICIENCY VIRUS-1 INFECTION
Human immunodeficiency virus 1 (HIV) infects myeloid cells in the central nervous system (CNS) and establishes a reservoir that persists despite antiretroviral therapy (ART). Infection leads to a 30-50% risk of developing HIV-associated neurocognitive disorders (HAND), a collection of mood, motor, …
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Characterisation of primary cilia in human hypothalamic neurons
… from the plasma membrane of most mammalian cells, including neurons. Among their roles, they are recognised to be involved in the control of feeding and energy expenditure by the hypothalamus. However, how cilia exert their role as signalling hubs in those neurons remains largely unknown. We …
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