Cell and Developmental Biology Commons^™

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Regulation Of Genome Architecture By Chromatin Remodeling In The Brain, Jared Vega Goodman

Arts & Sciences Electronic Theses and Dissertations

Brain development requires exquisite control of gene expression to establish and refine the proper circuitry of the nervous system. Gene expression control is under the purview of several cellular processes, including chromatin regulation in the form of DNA modification, histone modification, and nucleosome remodeling. Chromatin remodeling enzymes are the major effectors of nucleosome remodeling. These enzymes are clearly involved in brain development – mutations in chromatin remodeling enzymes are likely causative for neurodevelopmental disorders of cognition. Chromatin remodeling enzymes have discrete molecular functions and binding profiles and similarly control distinct phases of nervous system maturation. Chd4 is a Chd family …

Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland

Electronic Thesis and Dissertation Repository

ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in Atrx^Foxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …

From Single Cells To Human Disease: High-Resolution Phenotyping Of Male Infertility Models Using Single-Cell Rna Sequencing, Min Jung

Arts & Sciences Electronic Theses and Dissertations

Male infertility is a complex disease that can result in significant emotional distress and treatment costs. Globally, male infertility affects 7% of males, and while its incidence is rising, its etiology remains elusive. In order to improve patient care, it is critical to identify the nature of spermatogenic failure in as many men as possible. The extensive cellular heterogeneity of testis has limited the application of bulk expression measurements to capture crucial information to dissect molecular mechanisms of defects in the infertile patients. Thus, the application of single-cell RNA-sequencing on male germ cells provides an amazing new set of scientific …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Modification Of Ontogenic Expression Due To Relocation Of The Ry+ Gene In Drosophila Melanogaster, Allen A. Badgett Jr.

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The ry⁺ gene of Drosophila melanogaster and its associated enzyme, xanthine dehydrogenase, were employed in an analysis of the relationship between regulation and the location of a gene in the genome. Enzyme assays as an indication of gene activity were performed on genotypes containing zero, one and two doses of ry⁺ genes. Xanthine dehydrogenase activity of rosy genes in normal and relocated positions was determined during development.

The results indicate: 1) the gene ry⁺ is differentially active during ontogeny; 2) the activity during ontogeny is proportional to the number of ry⁺ genes present in the genome; …