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Articles 1 - 22 of 22
Full-Text Articles in Cell Biology
Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang
Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang
School of Medicine
Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA+), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …
Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja
Neonatal Islet-1+ Cardiovascular Progenitor Cell-Derived Exosomes And Their Functional Ability To Regulate Proliferation, Lourdes Ceja
Electronic Theses, Projects, and Dissertations
Heart failure affects many people around the world and can lead to disease progression and death. Consequently, new stem and exosome-based therapies are needed to address this major health issue and to provide therapeutic options that will improve outcomes for the increasing number of patients with heart disease. Stem cell-derived exosomes have captivated researchers’ attention over the past couple of years based on their functional role in cellular signaling which highlights the vital component of the secretome of stem and progenitor cells. Since neonates have significantly enhanced regenerative ability, we hypothesized that exosomes isolated from Islet-1+ expressing neonatal human cardiovascular …
Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie
Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie
Cal Poly Humboldt theses and projects
Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …
Probing The Role Of Astrocytes In The Pathology Of Fragile X Syndrome With Human Stem Cells, Baiyan Ren
Probing The Role Of Astrocytes In The Pathology Of Fragile X Syndrome With Human Stem Cells, Baiyan Ren
Theses & Dissertations
Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder related to intellectual disability and the most common monogenic cause of autism spectrum disorder. FXS is mainly caused by an expansion of CGG repeats in the 5’-untranslated region of fragile X mental retardation 1 (FMR1) gene, leading to the loss of expression of fragile X mental retardation protein (FMRP). Astrocytes are the most abundant glial cells in the central nervous system (CNS). Loss of FMRP in astrocytes has been found to contribute to structural and functional synaptic deficits in the Fmr1-KO mouse model. The contribution of human astrocytes, however, to the …
Cop9 Signalosome Component Csn-5 Promotes Accumulation And Function Of Stem Cell Regulators Fbf-1 And Fbf-2, Emily Osterli
Cop9 Signalosome Component Csn-5 Promotes Accumulation And Function Of Stem Cell Regulators Fbf-1 And Fbf-2, Emily Osterli
Graduate Student Theses, Dissertations, & Professional Papers
RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for stem cell maintenance in C. elegans, although the mechanisms by which FBFs protein levels are regulated remain unknown. Using a yeast two-hybrid screen, we identified an interaction between both FBFs and CSN-5, a component of the COP9 (constitutive photomorphogenesis 9) signalosome. This highly conserved COP9 complex can affect protein stability through a range of mechanisms including deneddylation, deubiquitination, and phosphorylation (Wolf et al., 2003). Mapping protein-protein interactions between FBFs and CSN-5 suggested that the MPN (Mpr1/Pad1 N-terminal) metalloprotease domain of CSN-5 interacts with the RNA-binding domain of FBFs at physiologically …
A Micro-Optic Stalk (Muos) System To Model The Collective Migration Of Retinal Neuroblasts, Stephanie Zhang, Miles Markey, Caroline D. Pena, Tadmiri Venkatesh, Maribel Vasquez
A Micro-Optic Stalk (Muos) System To Model The Collective Migration Of Retinal Neuroblasts, Stephanie Zhang, Miles Markey, Caroline D. Pena, Tadmiri Venkatesh, Maribel Vasquez
Publications and Research
Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes …
Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng
Theses & Dissertations
Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …
Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer
Platiscity Of C. Elegans Germline Stem Cells Under Nutritional And Metabolic Stress, Kenneth Trimmer
Dissertations & Theses (Open Access)
Stem cells are integral for tissue maintenance and fertility. Therefore, understanding how stem cells are regulated under stress is imperative. When confronted with acute starvation, stem cells must conserve energy and metabolites to cope with the lack of an external source. Caenorhabditis elegans germline stem cells (GSCs) are an excellent model for studying stem cell properties and regulation as they can divide throughout the life of the organism. While GSCs are an adult stem cell population, their cell cycle structure more closely mimics mouse and human embryonic stem cells with short G1 and long S phases. In this thesis, I …
Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley
Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley
Bioelectrics Publications
Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles …
Transcending The Cell Fate Stereotype: Cell Penetrating Peptide Technology Helps Induce Pluripotency In Multiple Cell Types, Kelsey Clearman
Transcending The Cell Fate Stereotype: Cell Penetrating Peptide Technology Helps Induce Pluripotency In Multiple Cell Types, Kelsey Clearman
Master of Science in Integrative Biology Theses
Induced pluripotent stem cells (iPSCs) are one of the most promising new technologies in the field of regenerative medicine. iPSCs can be generated directly from a patient’s own fibroblast cells then converted into any cell type, thus overcoming challenges associated with embryonic stem cells and graft-vs-host disease that result from current methods. Generation of iPSCs from fibroblasts is traditionally accomplished by ectopic expression of four key transcription factors (TFs): Oct4, Sox2, Klf4, and c-Myc also known as OSKM. These TFs have been shown to be involved in maintaining pluripotency and inhibiting embryonic stem (ES) cell differentiation. Reprogramming fibroblasts into iPSCs …
Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald
Evidence For The Involvement Of Runx1 And Runx2 In Maintenance Of The Breast Cancer Stem Cell Phenotype, Mark Fitzgerald
Graduate College Dissertations and Theses
In the United States, metastatic breast cancer kills approximately 40,000 women and 400 men annually, and approximately 200,000 new cases of breast cancer are diagnosed each year. Worldwide, breast cancer is the leading cause of cancer deaths among women. Despite advances in the detection and treatment of metastatic breast cancer, mortality rates from this disease remain high because the fact is that once metastatic, it is virtually incurable. It is widely accepted that a major reason breast cancer continues to exhibit recurrence after remission is that current therapies are insufficient for targeting and eliminating therapy-resistant cancer cells. Emerging research has …
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers
Electronic Theses and Dissertations
Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and …
Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson
Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson
Health Sciences and Kinesiology Faculty Articles
FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9OB −/−). Both Fgf9 knockout (Fgf9OB −/−) and the Fgf9 floxed littermates (Fgf9fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three …
Expansion, Characterization, Differentiation, And Visualization Of Mc 3t3-E1 Preosteoblast Cells: An In Vitro Model To Study Bone Healing And Stem Cell-Mediated Regeneration, Jakob T. Samsel, Madhu Dhar, Austin Bow, Tom Masi
Expansion, Characterization, Differentiation, And Visualization Of Mc 3t3-E1 Preosteoblast Cells: An In Vitro Model To Study Bone Healing And Stem Cell-Mediated Regeneration, Jakob T. Samsel, Madhu Dhar, Austin Bow, Tom Masi
Chancellor’s Honors Program Projects
No abstract provided.
Investigating The Fibroblastic Origin Of Skin-Derived Precursors And The Role Of Ccn2 As A Mediator Of Myofibroblastic Differentiation, Matthew Tsang
Investigating The Fibroblastic Origin Of Skin-Derived Precursors And The Role Of Ccn2 As A Mediator Of Myofibroblastic Differentiation, Matthew Tsang
Electronic Thesis and Dissertation Repository
Skin-derived precursors (SKPs) are defined as multipotent spheroid-forming cells cultured from the dermis that express markers of neural crest origin. Recent evidence suggests that tissue fibrosis can occur through the differentiation of progenitor cells into smooth muscle-like myofibroblasts. CCN2, a marker and mediator of fibrosis, is highly expressed during myofibroblast differentiation and is required for skin fibrogenesis. Here, I clarify the cellular origin of SKPs, and the molecular contribution of CCN2 in the myofibroblastic differentiation of SKPs. Using lineage tracing, I show that SKPs originate primarily from Col1a2-expressing dermal fibroblasts. Furthermore, I show that differentiation of SKPs into myofibroblasts requires …
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
The Role Of Stem Cells In Adipose Tissue Remodeling., Candice Reshay Holden 1988-
Electronic Theses and Dissertations
The work presented in this dissertation outlines the role of stem cells in the remodeling of adipose tissue under conditions of nutrient excess. Obesity-induced variations in adipose tissue stem cell distribution were uncovered by analysis of the stromal vascular fraction isolated from mice fed a high fat diet for several weeks. Bone marrow cell transplantation was used to determine the derivation of progenitor cells found in adipose tissue; and supplementation of depleted progenitor cell populations achieved via direct cell transplantation, helped to determine the contribution of these progenitor cells to the remodeling process. The dissertation is presented in five chapters …
The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller
The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller
Student Publications & Research
CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in …
Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli
Isolation And Characterization Of Multipotent Lung Stem Cells From P53 Mutant Mice Models, Venkat Sundar Gadepalli
Theses and Dissertations
Recent advances in understanding lung biology have shown evidence for the existence of resident lung stem cells. Independent studies in identifying and characterizing these somatic lung stem cells have shown the potential role of these cells in lung repair and regeneration. Understanding the functional characteristics of these tissue resident stem/progenitor cells has gained much importance with increasing evidence of cancer stem cells, cells in a tumor tissue with stem cell characteristics. Lung cancer is most commonly characterized by loss of p53 function which results in uncontrolled cell divisions. Incidence of p53 point mutations is highest in lung cancer, with a …
Germline Transgenic Methods For Tracking Cells And Testing Gene Function During Regeneration In The Axolotl, Shahryar Khattak, Maritta Schuez, Tobias Richter, Dunja Knapp, Saori L. Haigo, Tatiana Sandoval-Guzmán, Kristyna Hradlikova, Annett Duemmler, Ryan R. Kerney, Elly M. Tanaka
Germline Transgenic Methods For Tracking Cells And Testing Gene Function During Regeneration In The Axolotl, Shahryar Khattak, Maritta Schuez, Tobias Richter, Dunja Knapp, Saori L. Haigo, Tatiana Sandoval-Guzmán, Kristyna Hradlikova, Annett Duemmler, Ryan R. Kerney, Elly M. Tanaka
Biology Faculty Publications
The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum(axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly …
Induced-Pluripotent Stem-Derived Neuronal Progenitor Cells As A Novel Treatment For Neurodegenerative Diseases, Dennisse A. Gonzalez-Romero
Induced-Pluripotent Stem-Derived Neuronal Progenitor Cells As A Novel Treatment For Neurodegenerative Diseases, Dennisse A. Gonzalez-Romero
Dissertations & Theses (Open Access)
Cellular therapies, as neuronal progenitor (NP) cells grafting, are promising therapies for patients affected with neurodegenerative diseases like Creutzfeldt-Jakob Disease (CJD). At this time there is no effective treatment or cure for CJD. The disease is inevitably fatal and affected people usually die within months of the appearance of the first clinical symptoms. Compelling evidence indicate that the hallmark event in the disease is the conversion of the normal prion protein (termed PrPC) into the disease-associated, misfolded form (called PrPSc). Thus, a reasonable therapeutic target would be to prevent PrP misfolding and prion replication. This strategy …
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel
CMC Senior Theses
The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …
Characterization And Differentiation Of Peripheral Blood Derived Multipotent Adult Progenitor Cells, Hari Satya Shankar Addagarla
Characterization And Differentiation Of Peripheral Blood Derived Multipotent Adult Progenitor Cells, Hari Satya Shankar Addagarla
Theses, Dissertations and Capstones
Stem cells are populations of undifferentiated cells that are found in most tissues and act as precursors for regeneration and maintenance. In the future, they could provide promising therapies for diseases which are to date incurable. Our lab developed a novel cell line from the peripheral blood of adult transgenic green fluorescent protein swine and designated them as Peripheral Blood Derived Multipotent Adult Progenitor Cells (PBD-MAPCs). In this study we characterized the mRNA and protein expression profiles of PBD-MAPCs before and after neural differentiation and investigated the potential of PBD-MAPCs to differentiate into myocardial or neural lineages in vitro. We …