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 23 for “"single nuclei"”.
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Investigating iPSC-Derived Macrophage Stimulation with Oxidised Low-Density Lipoprotein as an Effective In Vitro Model of Foam Cells in Atherosclerosis
… potential foam cell-like populations using single cell RNA sequencing (scRNA-seq) of plaques, however due to known limitations of whole cell and more recent findings expanding our current knowledge of foam cell biology, much remains to be explored. Foam cells can be generated in vitro by …
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Epithelial cell plasticity in chronic liver disease (MASLD/NAFLD)
… the transdifferentiation hypothesis. I then use single nuclei RNA sequencing analysis from liver biopsies to capture and characterise the transcriptomic signature of those biphenotypic cells. Next, for the second part of the dissertation, I confirm that cholangiocyte organoids can be derived from …
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Compensation Between Foxp Transcription Factors Maintains Proper Striatal Function
… to regulation of downstream targets genes using single-nuclei RNA-seq and found that in both juvenile and adult D1-SPNs, loss of both transcription factors resulted in differential expression of hundreds of genes (Chapter Four). I was able to use these experiments to also investigate how loss of …
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Identifying unique cell states in early liver oncogenesis with transcription coupled repair
… are predisposed to tumour formation, I conducted single nuclei RNA sequencing post-DEN treatment and compared the transcriptional profiles of groups and of single nuclei to the mutational data. I show that a subset of DEN-damaged Cyp2e1 expressing hepatocytes has the best expression fit with the …
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Molecular Mechanisms of Opioid Use Disorder in Human Brain Models
… of many neuron-correlated synaptic genes. Using single-nuclei RNA sequencing, I found global suppression of cell-cell signaling networks across all cell types, particularly involved in synaptic and growth factor signaling. Finally, using a novel postmortem fibroblast-derived induced pluripotent …
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Towards dissecting neural ensembles : development of genetic profiling and targeting approaches
… ensembles. First, we present the development of single nuclei RNA sequencing methods and the application of the methods to chart the cellular diversity and its signature gene expression patterns in the adult mouse hippocampus. Second, we introduce rational design and predictable implementation of …
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Exploring the gene regulatory dynamics of the maturing human brain
… to the current brain cell atlas with pediatric single cell data. Bio-banked pediatric and adult brain tissue samples, obtained during surgery to treat epilepsy, were used to optimise and generate a nuclei isolation protocol. Single nuclei RNA-seq (snRNA-seq) libraries were generated using the …
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The Role of the Circadian Clock in the Paraventricular Nucleus of the Hypothalamus in Diurnal Energy Balance
… immunoprecipitation followed by sequencing and single nuclei RNA sequencing (snRNA-seq), we analyzed the genomic and transcriptional regulation by BMAL1 across time and in PVN cell types. Our study reveals not only rhythmic binding at specific loci by BMAL1, but that loss of BMAL1 results in …
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Stromal interactions in pleural mesothelioma
… It is a stromal rich malignancy with cancer cell nuclei frequently accounting for less than 25% of all tumour nuclei. The remainder are largely comprised of stromal cells, the roles of which have been relatively neglected by existing studies. Of particular interest are the cancer-associated …
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Integrated Analysis of Molecular and Clinical Features in Melanoma Patients with Brain Metastases
… was defined at the transcriptomic level using single-cell RNA-seq, single-nuclei RNA-seq, and spatial transcriptomics (ST) technologies. Together these results support the clinical significance of specific molecular and immune features of MBMs and suggest their potential use for developing …
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White Adipose Tissue Remodeling by Intermittent Fasting
… and expansion of pro-adipogenic APs. Single-nuclei sequencing analysis revealed significant enrichment of circadian pathway within the APs, which could be a key mediator of IF-induced WAT remodeling. Interestingly, animal models with circadian disruption exhibited higher WAT mass and …
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The development and use of cutting edge next generation sequencing methodologies to study RNA viruses
… changes respectively. We have also used single nuclei RNA sequencing (snRNA-Seq) for a more granular look at transcriptomic changes using the package Seurat in R. As the 2015-2016 Zika virus (ZIKV) outbreak in S. America was associated with development of microcephaly in infants born to …
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Investigating Metastatic Lineage In Colorectal Cancer By Single Cell Dna Sequencing
… problem, we have developed a highly-multiplexed single cell DNA sequencing method that combines flow-sorting of single nuclei, multiple-displacement-amplification using Φ29 polymerase, low-input library preparation, library barcoding, targeted capture and NGS to generate high-coverage data from …
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DNA G-quadruplex structures in human cancer cells
… were associated with copy number aberrations and single-nucleotide variants, as well as common breast cancer driver regions, suggesting a link between cancer genome instability and G4 structure formation. Subsequently, to increase the versatility of G4 profiling, I developed G4-Cleavage Under …
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Integrative multiomic insights into Alzheimer’s disease pathology
… DNA misrepair, and validated this hypothesis in single-nuclei genome sequencing data from AD patients. I observed an imbalance in the nucleotide pool and showed that pharmacological or genetic enhancement of nucleotide metabolism is neuroprotective in AD. In Chapter 5, I conducted a proteomics …
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Selective Neuronal Vulnerability in Neocortices from Patients with C9ORF72-related Neurodegeneration
… not yet been performed. With recent advances in single-cell and spatial transcriptomic approaches, our hypothesis can now be investigated in an unbiased fashion and at unprecedented resolution. The work in this thesis focuses on identifying selectively vulnerable neurons in the post-mortem …
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Mapping the Feeding Circuitry in the Mouse and Human Brain
… To map the mouse hindbrain, we performed single nucleus RNA sequencing on hindbrain samples from mice fed *ad libitum* and mice subjected to an overnight fast. Here, we profile 16,034 single nuclei, and demonstrate the oligodendrocytes are transcriptionally sensitive to an overnight fast. …
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Investigation into the Neurogenetics of Vocal Learning in Tursiops Truncatus, the Bottlenose Dolphin
… (LMC) and functionally analogous vocal learning nuclei in songbirds (HVC and RA). To screen for the putative “vocal learning” specialized subregion of the identified dolphin motor cortex, we conducted double-label Fluorescent in Situ Hybridization (FISH) experiments for SLIT1, a downregulated …
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Quantitative spatial transcriptomics of the developing brain
… heterogeneity across large tissue areas at a single-cell level are lacking. Applying this capability to the developing brain would enable reconstruction of a full spatial transcriptomic map of neural heterogeneity and the discovery of novel regional neural subtypes with potential functional …
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Myc and Cyclin T1 co-expression as a therapeutic strategy for cardiac repair following myocardial infarction
… to functional improvement. Methods Whole-heart single-nuclei RNA sequencing (snRNAseq), in vivo experiments, histology methods, and molecular biology techniques were used to assess Myc and Ccnt1 induced cardiomyocyte-specific gene expression changes, validate cardiomyocyte cell cycle …
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