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Articles 1 - 13 of 13
Full-Text Articles in Life Sciences
Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah
Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah
Electronic Thesis and Dissertation Repository
Myogenesis is defined as the formation of skeletal muscle tissue during embryonic development and involves a multitude of cellular signalling pathways. Among these include the Sonic hedgehog (Shh) signalling pathway which must be deactivated for differentiation into muscle cells to occur. However, less is known regarding the pathways operation during cell differentiation and whether Suppressor of Fused (SUFU), the protein inhibitor of Shh signalling, plays a role. To address this, mouse C2C12 myoblast cells were utilized as a model and differentiated into muscle cells to identify the presence of SUFU during this time. Experiments in qRT-PCR show a decrease in …
Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie
Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie
Electronic Thesis and Dissertation Repository
The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of the epiblast (EPI) and primitive endoderm (PrE). Understanding the process of cell fate specification is crucial to appreciate the intricacies of proper embryonic development. While the mouse embryo is an excellent model, limitations do exist with number, technical challenges, and accessibility, therefore, in my thesis I employed two cell-based models to recapitulate the EPI-PrE fate in vitro. Many signaling pathways have been implicated in this lineage decision, metabolism and its downstream products have been recently regarded as a driver of lineage commitment. Using various biochemical, molecular, …
Characterising The Role Of Ovol1 In Cell Growth Regulation, Maram Albakri
Characterising The Role Of Ovol1 In Cell Growth Regulation, Maram Albakri
Electronic Thesis and Dissertation Repository
The placenta supports the exchange of nutrients and gases between mother and fetus. Trophoblasts are the parenchymal cells of the placenta and perform the vast majority of its functions. There are different types of trophoblasts derived from stem cells called cytotrophoblasts (CTs). The balance between CT proliferation and differentiation is important for placental development. OVO-like 1 (OVOL1) is a transcription factor expressed in many epithelial lineages undergoing differentiation, including human differentiating CTs. The molecular mechanisms through which OVOL1 represses proliferation and/or promotes differentiation are unknown. We hypothesize that OVOL1 interacts with specific HDACs to repress CT proliferation. Ectopically expressing OVOL1 …
Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain
Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain
Electronic Thesis and Dissertation Repository
Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …
Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert
Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert
Electronic Thesis and Dissertation Repository
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) with retinoic acid (RA) treatment, resulting in up-regulation of Gata6, which when translated directly activates Wnt6. Canonical Wnt signalling is required for PrE differentiation, and this, like most developmental processes, requires input from one or more additional pathways, including hedgehog (Hh). The Hh pathway is regulated by GATA6, and crosstalks positively/negatively with Wnt signalling. Ihh up-regulation in F9 cells accompanies PrE induction, but a role for GATA6 or Hh pathway activation in obligatory Wnt/ß-catenin signalling is not known. To address this, I show that RA induces Ihh and altered expression of …
Distinct Roles Of Gaba(A)R Signaling In The Regulation Of Two Human T Lymphocyte Lines, Ying Lin
Distinct Roles Of Gaba(A)R Signaling In The Regulation Of Two Human T Lymphocyte Lines, Ying Lin
Electronic Thesis and Dissertation Repository
In response to antigen presentation, helper T lymphocytes (TH cells) initiate store-operated Ca2+ entry (SOCE) and differentiate into effector subtypes such as TH1 and TH2 cells. These cells play essential roles in adaptive immunity and the pathogenesis of various autoimmune and allergic diseases. The differentiation and activity of TH cells are also critically regulated by paracrine and autocrine soluble factors in the cell microenvironment. Previous studies have reported that TH cells produce gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD) and express A-type GABA receptors (GABAARs), forming an autocrine GABA …
Cell Signaling Crosstalk And Differentiation Of F9 Cells Into Extraembryonic Endoderm, Gurjoth Singh Deol
Cell Signaling Crosstalk And Differentiation Of F9 Cells Into Extraembryonic Endoderm, Gurjoth Singh Deol
Electronic Thesis and Dissertation Repository
Mouse F9 cells differentiate into primitive endoderm (PrE) when treated with retinoic acid (RA). During PrE differentiation the canonical Wnt signaling pathway is known to play an integral role in the process. In addition to Wnt signaling, there have been implications that the Hedgehog (Hh) pathway may also be involved. Previous results show that the Indian Hedgehog (Ihh) gene is upregulated during RA-induced differentiation; however further details of Hh signaling during PrE differentiation have yet to be discovered. A Gli-luciferase construct indicated that Hh signaling increases during RA-induced differentiation, implicating that the pathway is involved in PrE formation. Inhibiting …
The Role Of Nadph Oxidase In Ros Mediated Differentiation, Benjamin J. Dickson
The Role Of Nadph Oxidase In Ros Mediated Differentiation, Benjamin J. Dickson
Electronic Thesis and Dissertation Repository
Mouse teratocarcinoma F9 cells differentiate into primitive endoderm (PrE) when treated with retinoic acid (RA) or H2O2 and these changes are accompanied by an upregulation of Wnt6 and activation of the canonical WNT/β-catenin pathway. Data from our lab shows PrE differentiation is accompanied by an increase in reactive oxygen species (ROS), which induces a conformational change in Nucleoredoxin preventing its ability to bind and inhibit Dishevelled. This in turn positively impacts on the WNT/β- catenin signaling pathway leading to differentiation. The source of endogenous ROS seen following RA treatment was investigated and members of the NADPH oxidase (NOX) family were …
The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki
The Ctcf Chromatin Organizer Is Required For Hindlimb Development, Katherine L. Rabicki
Electronic Thesis and Dissertation Repository
Mutations in chromatin organizer CTCF were identified in patients with intellectual disability and skeletal defects. Previous studies demonstrated that depletion of CTCF in murine limb mesenchyme results in apoptosis in the forelimb. The role of CTCF in the hindlimb, however, is unknown. My objective was to investigate effects of CTCF deletion on chondrogenesis and skeletal development in the hindlimb. In vitro wild-type micromass cultures demonstrate that chondrocyte gene expression is delayed in the hindlimb when compared to forelimbs. Embryonic CtcfFl/Fl;Prx1Cre mice were investigated, and qRT-PCR and histology were performed on limb buds and long bones. Results show that …
Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin
Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin
Electronic Thesis and Dissertation Repository
ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects …
Targeted Proteomics Of Human Pluripotent Stem Cells, Kevin Gregory Kania
Targeted Proteomics Of Human Pluripotent Stem Cells, Kevin Gregory Kania
Electronic Thesis and Dissertation Repository
Human pluripotent stem cells (hPSCs) exhibit two unique characteristics: pluripotency and self-renewal. These properties are maintained by a series of complex signaling pathways, however, quantitative data for the respective proteins is lacking. Selected reaction monitoring (SRM) is a targeted, quantitative technique in mass spectrometry that is highly sensitive in peptide detection. In this thesis, an SRM protocol was developed in order to detect and quantify a defined set of proteins responsible for maintaining stem cell pluripotency. Two hESC differentiation protocols were validated for use as model systems within which to measure differential protein expression by SRM. SRM assays were generated …
The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef
The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef
Electronic Thesis and Dissertation Repository
The human placenta of different gestational ages is a readily available source for isolation of adult mesenchymal stem cell (MSC) for potential use in regenerative therapies. The chorionic villous region, the largest component of a placenta that interfaces with the maternal circulation, is a rich source of placental MSCs (PMSCs). To remain multipotent, PMSCs are best maintained in culture conditions that mimic the in vivo microenvironment. Insulin like growth factors (IGFs, IGF-I and -II) and oxygen tension are two of the most important microenvironmental factors in the placenta. They are of low concentration or tension respectively, at early gestation, and …
Nucleoredoxin And Wnt Signaling In F9 Cells, Leanne Sandieson
Nucleoredoxin And Wnt Signaling In F9 Cells, Leanne Sandieson
Electronic Thesis and Dissertation Repository
Nucleoredoxin is a redox sensitive protein recently shown to be involved in the Wnt/β-catenin pathway through binding dishevelled. When Wnt is present, dishevelled prevents a destruction complex from degrading β-catenin. This facilitates the translocation of β-catenin into the nucleus where it binds to TCF-LEF to impart changes in gene expression. This study used mouse F9 cells as a model to examine whether or not nucleoredoxin is involved in augmenting the Wnt/β-catenin signaling required for extraembryonic endoderm differentiation. It was found that nucleoredoxin and three dishevelled isoforms were present in F9 cells. Furthermore, nucleoredoxin was found to bind to dishevelled-2, and …