Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
Mitophagy-Mediated Regulation Of Ros Homeostasis During Hsc Activation Contributes To Cell Fate, Amber Lynne Smith
Mitophagy-Mediated Regulation Of Ros Homeostasis During Hsc Activation Contributes To Cell Fate, Amber Lynne Smith
Theses and Dissertations (ETD)
The ability of hematopoietic stem cells to self-renew and differentiate is required for the maintenance of all blood lineages under basal physiologic conditions and in response to inflammatory stress. The degradative capacity of the autophagy-lysosomal system is a determinant of hematopoietic stem cell (HSC) activation status with low autophagy predicting activation of HSCs, and autophagy deficiency causing the spontaneous loss of quiescence and HSC exhaustion. Although an increase in mitochondrial activity has been suggested as the cause of HSC depletion in autophagy-defective models, the contribution of mitophagy to HSC function remains to be elucidated. Here, we capitalized on the observation …
Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson
Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson
Theses and Dissertations (ETD)
Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …
The Characterization Of Hematopoiesis In Murine Fetal Bone Marrow, Trent Daniel Hall
The Characterization Of Hematopoiesis In Murine Fetal Bone Marrow, Trent Daniel Hall
Theses and Dissertations (ETD)
Hematopoietic stem cells (HSCs) and their downstream progenitors are a heterogeneous population of cells that are indispensable for lifelong hematopoiesis and are often utilized in the clinic for the treatment of hematologic maladies via hematopoietic stem cell transplantation (HSCT). Over several decades, it has been discovered that HSCs arise in the dorsal aorta of the developing embryo, migrate to the fetal liver (FL), and undergo a large expansion before reaching their final resting place in the bone marrow (BM). Many resources have been invested in understanding the roles of the different niches HSCs encounter along their journey. A greater understanding …
Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar
Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar
Theses and Dissertations (ETD)
The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Theses and Dissertations (ETD)
Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …