subject:(Hematopoiesis)

University of Utah

1. Huang, Xiaosong. Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment.

Degree: PhD, Pathology;, 2010, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1204/rec/355

► Cell differentiation is influenced by a combination of cues from both extracellular and intracellular sources. Recent advances in the regulation of hematopoiesis have focused on… (more)

Subjects/Keywords: Hematopoiesis; Copper

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APA (6^th Edition):

Huang, X. (2010). Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1204/rec/355

Chicago Manual of Style (16^th Edition):

Huang, Xiaosong. “Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment.” 2010. Doctoral Dissertation, University of Utah. Accessed March 04, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1204/rec/355.

MLA Handbook (7^th Edition):

Huang, Xiaosong. “Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment.” 2010. Web. 04 Mar 2021.

Vancouver:

Huang X. Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2021 Mar 04]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1204/rec/355.

Council of Science Editors:

Huang X. Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1204/rec/355

2. Lim, Yiting. Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications.

Degree: 2014, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/37983

► Certain cancers, especially those occurring in the hematopoietic system, can be identified by their cell of origin, and share many similar properties and signaling pathways… (more)

▼ Certain cancers, especially those occurring in the hematopoietic system, can be identified by their cell of origin, and share many similar properties and signaling pathways to their normal counterparts. We use the hematopoietic system to interrogate the relationship between normal and neoplastic transformation. This work aims to better understand the molecular mechanisms of disease transformation in hematologic malignancies and translate basic biology findings into potential clinical applications. To examine how normal hematopoiesis is perturbed, we investigated how low dose-rate radiation affected hematopoietic cells in a whole animal model, and uncover mechanisms to mitigate this adverse effect. Although the effects of acute radiation exposure have been well studied for many years, it is likely that widespread life-threatening radiation incidents will occur in the form of lethal doses delivered at relatively low rates over protracted time periods. We show that damage to hematopoietic progenitors and hematopoietic failure is a consequence of such radiation exposure. In addition, the anti-malaria agent chloroquine can protect these hematopoietic progenitors by activating ATM, a key player in the DNA damage response pathway, thus enhancing overall survival. We provide a mechanistic explanation and potentially viable prophylaxic therapy for protracted low dose-rate radiation induced death. The Hedgehog signaling pathway is highly conserved and important for development. Though its role in normal hematopoiesis is controversial, it does not impact normal adult hematopoiesis. Hedgehog signaling is aberrantly regulated in many cancers, including several hematopoietic malignancies. We found Hedgehog signaling to be upregulated in human secondary leukemias. We hypothesize that Hedgehog signaling plays a role in disease progression and generated a novel transgenic mouse model of myeloid disease progression. Conditional activation of Hedgehog signaling dramatically accelerated disease progression from a chronic myeloproliferative disorder initiated by an activating mutation in the FLT3 tyrosine kinase receptor to rapidly fatal acute myeloid leukemia. Mice harboring both the FLT3-ITD (a commonly found mutation in adult AML) and SmoM2, (a constitutively active form of Smoothened) alleles died rapidly from AML caused by increased myeloid progenitor proliferation. Pharmacologically inhibiting both Hedgehog and FLT3 pathways synergistically reduced leukemic growth and improved overall survival compared to targeting either pathway alone. Advisors/Committee Members: Small, Donald (advisor).

Subjects/Keywords: Hematopoiesis; leukemia

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APA (6^th Edition):

Lim, Y. (2014). Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37983

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lim, Yiting. “Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications.” 2014. Thesis, Johns Hopkins University. Accessed March 04, 2021. http://jhir.library.jhu.edu/handle/1774.2/37983.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lim, Yiting. “Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications.” 2014. Web. 04 Mar 2021.

Vancouver:

Lim Y. Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Mar 04]. Available from: http://jhir.library.jhu.edu/handle/1774.2/37983.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lim Y. Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37983

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

3. Notta, Faiyaz. Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies.

Degree: 2011, University of Toronto

URL: http://hdl.handle.net/1807/31884

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The overall aim of my thesis is to gain insight into the cellular and molecular basis of the hierarchical organization of the human blood system,… (more)

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The overall aim of my thesis is to gain insight into the cellular and molecular basis of the hierarchical organization of the human blood system, and how these normal development processes are subverted into leukemogenesis. To date, the major cellular classes that comprise human blood remain ill defined as rigorous clonal analysis required to define the self-renewal and lineage potential of single cells has not yet been performed. Here, identification CD49f as a novel marker of human HSC led to the ability to transplant single human HSC in NOD-scid IL2Rgc-/- mice. Loss of CD49f and Thy1 uniquely demarcated multi-potent progenitors (MPP) from HSC. The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision during lineage restriction from HSC. The validity of this model in the mouse has been questioned; however, little is known about the lineage potential of human progenitors. By clonally mapping the developmental potential of seven progenitor classes from neonatal cord blood and adult bone marrow, human multi-lymphoid progenitors (MLP) were identified as a distinct population of Thy1-/loCD45RA+ cells in the CD34+CD38- stem cell compartment that can give rise to all lymphoid cell types, as well as monocytes, macrophages and dendritic cells. This indicates that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. While non-genetic mechanisms govern cell-fate commitment and lineage specification, hematopoietic malignancies are often initiated by aberrant gene rearrangements that can subvert normal cellular processes. Full transformation requires the accumulation of multiple genetic lesions. Most tumours exhibit dramatic genetic heterogeneity downstream of the initiating oncogenic event and are composed of pockets of genetically distinct clonal subpopulations. However little is known of how diversity evolves or the impact diversity has on functional properties. Here, using xenografting and DNA copy number alteration (CNA) profiling of human BCR-ABL1 lymphoblastic leukaemia, it was demonstrated that genetic diversity occurs in functionally defined leukaemia-initiating cells (L-IC) and that many diagnostic patient samples contain multiple genetically distinct L-IC subclones. Reconstructing the subclonal genetic ancestry of several samples by CNA profiling demonstrated a branching multi-clonal evolution model of leukaemogenesis, rather than linear succession. For some patient samples, the predominant diagnostic clone repopulated xenografts, while in others it was outcompeted by minor subclones. Reconstitution with the predominant diagnosis clone was associated with more aggressive growth properties in xenografts, deletion of CDKN2A/B, and a trend to poor patient outcome. Our findings link clonal diversity with L-IC function and underscore the importance of developing therapies that eradicate all intratumoural subclones.

PhD

Advisors/Committee Members: Dick, John E., Molecular and Medical Genetics.

Subjects/Keywords: hematopoiesis; leukemia; 0306

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APA (6^th Edition):

Notta, F. (2011). Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/31884

Chicago Manual of Style (16^th Edition):

Notta, Faiyaz. “Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies.” 2011. Doctoral Dissertation, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/31884.

MLA Handbook (7^th Edition):

Notta, Faiyaz. “Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies.” 2011. Web. 04 Mar 2021.

Vancouver:

Notta F. Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies. [Internet] [Doctoral dissertation]. University of Toronto; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/31884.

Council of Science Editors:

Notta F. Clonal Analysis of Normal and Malignant Human Hematopoietic Hierarchies. [Doctoral Dissertation]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/31884

Universiteit Utrecht

4. Lange, T.A.D. The role of Cdx in embryonic and adult mammalian hematopoiesis.

Degree: 2011, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/209132

► All blood cells orginate from a common stem cell in the bone marrow: the hematopoietic stem cell (HSC), which is characterized by two main properties:… (more)

▼ All blood cells orginate from a common stem cell in the bone marrow: the hematopoietic stem cell (HSC), which is characterized by two main properties: self-renewal and multipotency. Hematopoiesis is a hierarchical system with the HSC at the top. During embryogenesis, hematopoietic cells and progenitors with broader potentials are progressively generated. Mammalian hematopoietic development begins in extra-embryonic structures and continues within the embryo proper. In the conceptus, the mesoderm is patterned along the anterior-posterior (A-P) axis. The positional identity of the mesoderm on the A-P axis is regulated by Hox genes. Cdx genes, another homeobox gene family, are required for the posterior growth of axial tissues during development. Cdx genes are known to act upstream of Hox. The first evidence for a role for Cdx in hematopoiesis was established in zebrafish. Using embryoid bodies, it was shown that the Cdx genes promote embryonic hematopoiesis in the mouse by upregulating target Hox genes. Induction of Cdx4 promotes proliferation of hematopoietic progenitors. HSCs were more successfully derived from ESCs upon Cdx4 and Hoxb4 induction. Cdx gene deficiency jeopardizes embryonic hematopoiesis, with severe consequences for blood development upon Cdx2 mutations. As adult Cdx4 knockout mice only displayed minimal hematopoietic abnormalities, Cdx4 is dispensable for adult hematopoiesis. Previous studies on Cdx1 and Cdx2 mutants did not report any hematopoietic malformations either. However, it was demonstrated that overexpression of Cdx4 promotes leukemia in adult mice and that ectopic expression of Cdx2 is a key event in myeloid leukemia. The Cdx genes thus act as stimulators of hematopoietic progenitor maintenance and proliferation. Loss of function of Cdx impairs embryonic hematopoiesis, whereas gain of function in the adult bone marrow results in overproliferation of hematopoietic progenitors, which can instigate leukemia. Advisors/Committee Members: Deschamps, J..

Subjects/Keywords: hematopoiesis; mouse; Cdx; leukemia

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APA (6^th Edition):

Lange, T. A. D. (2011). The role of Cdx in embryonic and adult mammalian hematopoiesis. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/209132

Chicago Manual of Style (16^th Edition):

Lange, T A D. “The role of Cdx in embryonic and adult mammalian hematopoiesis.” 2011. Masters Thesis, Universiteit Utrecht. Accessed March 04, 2021. http://dspace.library.uu.nl:8080/handle/1874/209132.

MLA Handbook (7^th Edition):

Lange, T A D. “The role of Cdx in embryonic and adult mammalian hematopoiesis.” 2011. Web. 04 Mar 2021.

Vancouver:

Lange TAD. The role of Cdx in embryonic and adult mammalian hematopoiesis. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2021 Mar 04]. Available from: http://dspace.library.uu.nl:8080/handle/1874/209132.

Council of Science Editors:

Lange TAD. The role of Cdx in embryonic and adult mammalian hematopoiesis. [Masters Thesis]. Universiteit Utrecht; 2011. Available from: http://dspace.library.uu.nl:8080/handle/1874/209132

University of Rochester

5. Peslak, Scott Alan. Erythropoiesis: Injury and Recovery.

Degree: PhD, 2012, University of Rochester

URL: http://hdl.handle.net/1802/21468

► Erythropoiesis is a robust process of cellular expansion and maturation that is required to maintain the massive steady-state red blood cell mass. However, anemia is… (more)

▼ Erythropoiesis is a robust process of cellular expansion and maturation that is required to maintain the massive steady-state red blood cell mass. However, anemia is common following clastogenic injury such as total body irradiation (TBI), suggesting that erythroid progenitors and precursors may be highly sensitive targets of radiation. Here, we explore the endogenous injury and recovery processes of the erythron following 4 Gy TBI of C57BL/6 mice. Functional colony assays were used to analyze erythroid progenitors, including day 7 burst-forming units (d7 BFU-E) and more mature d3 BFU-E and colony-forming units (CFU-E), and imaging flow cytometry was utilized to quantify erythroblast precursors, consisting of immature proerythroblasts and progressively more mature basophilic, polychromatophilic, and orthochromatic erythroblasts. We find that essentially all bone marrow and splenic erythroid progenitors and precursors are lost within two days following 4 Gy TBI. Phenotypic CFU-E and proerythroblasts in the bone marrow exhibit preferential apoptotic loss immediately following sublethal irradiation, revealing a functional transition at the proerythroblast to basophilic erythroblast maturational stages characterized by a shift from a pro-apoptotic to an anti-apoptotic phenotype. Following this initial loss, erythroid recovery is characterized by specific expansion of late-stage erythroid progenitors (d3 BFU-E and CFU-E) in the bone marrow that is dependent on endogenous erythropoietin (EPO) induction. This robust progenitor expansion is followed by a wave of maturing erythroid precursors in the bone marrow and their transient emergence in the bloodstream before re-initiation of extramedullary erythropoiesis in the spleen. Furthermore, we find that bone marrow macrophages, which constitute the erythroid precursor microenvironmental niche, are relatively radioresistant and form robust erythroblast islands post-4 Gy TBI during erythroid precursor recovery. We conclude that sublethal radiation serves as a model of endogenous stress erythropoiesis that is characterized by specific injury to the extravascular erythron, initial expansion and maturation of EPO-responsive late-stage progenitors exclusively in the bone marrow, and subsequent reseeding of extramedullary sites. This model will facilitate the study of mechanisms regulating erythropoiesis in bone marrow and extramedullary sites as well as the functional evaluation of erythroid lineage-directed therapeutics to mitigate cellular injury.

Subjects/Keywords: Erythropoiesis; Hematopoiesis; Radiation; Erythroid Progenitor

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APA (6^th Edition):

Peslak, S. A. (2012). Erythropoiesis: Injury and Recovery. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/21468

Chicago Manual of Style (16^th Edition):

Peslak, Scott Alan. “Erythropoiesis: Injury and Recovery.” 2012. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/21468.

MLA Handbook (7^th Edition):

Peslak, Scott Alan. “Erythropoiesis: Injury and Recovery.” 2012. Web. 04 Mar 2021.

Vancouver:

Peslak SA. Erythropoiesis: Injury and Recovery. [Internet] [Doctoral dissertation]. University of Rochester; 2012. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/21468.

Council of Science Editors:

Peslak SA. Erythropoiesis: Injury and Recovery. [Doctoral Dissertation]. University of Rochester; 2012. Available from: http://hdl.handle.net/1802/21468

Loyola University Chicago

6. Birch, Noah Warren. Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity.

Degree: PhD, Molecular and Cellular Biochemistry Program, 2013, Loyola University Chicago

URL: https://ecommons.luc.edu/luc_diss/504

► TheMixed Lineage Leukemia(MLL) gene can participate in chromosomal translocations which generate a fusion protein leading to acute leukemia. A better understanding of how MLL… (more)

▼ TheMixed Lineage Leukemia(MLL) gene can participate in chromosomal translocations which generate a fusion protein leading to acute leukemia. A better understanding of how MLL fusion proteins contribute to leukemia is necessary in order to develop more effective treatments. In my dissertation project, I investigated the functional role of amino acids within the MLL CXXC domain to determine how specific residues contribute to leukemogenic capacity. MLL fusion proteins retain the amino-terminal portion of MLL including the CXXC DNA-binding domain while the carboxy-terminal portion is comprised of a fusion partner. The closest homolog of MLL, MLL2 (alternatively named MLL4), also contains a similar CXXC domain, yet an artificial MLL2 fusion protein is unable to transform cellsin vitro. I hypothesized that specific amino acid differences between the MLL and MLL2 CXXC domains account for differences in leukemogenic capacity. To test this hypothesis, the MLL2 CXXC domain was cloned into the context of the well-studied MLL-AF9 fusion protein to generate an artificial MLL/MLL2-AF9 chimera. Amino acid substitutions were then introduced within the MLL2 CXXC domain of this synthetic chimera to restore residues to the MLL sequence. By comparing residues of the MLL and MLL2 CXXC domains in colony formation and protein binding assays, critical amino acids were identified on both the DNA-binding surface and on the opposite, non-DNA-contact surface of the CXXC. Cysteine 1188 of the MLL CXXC domain is the only non-zinc-coordinating cysteine residue within the CXXC domain. This residue is critically positioned on the DNA-binding surface with susceptibility to post-translational modification. I hypothesized that the Cys1188 may be physiologically altered to regulate DNA-binding affinity. Transformed MLL-AF9 progenitor cells were treated with modifying agents or grown under conditions of varying oxygen concentration. The MLL-AF9 cells showed a modest susceptibility to parthenolide treatmentin vitrobut showed no significant differences in proliferation when grown under conditions of varying oxygen. The results from these studies build on the initial work conducted in our laboratory on the MLL CXXC domain and Cys1188 providing valuable direction for future investigations which may eventually allow for therapeutic targeting of the CXXC domain in MLL-associated leukemia.

Subjects/Keywords: Hematopoiesis; Leukemia; MLL; MLL2; Biochemistry

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APA (6^th Edition):

Birch, N. W. (2013). Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity. (Doctoral Dissertation). Loyola University Chicago. Retrieved from https://ecommons.luc.edu/luc_diss/504

Chicago Manual of Style (16^th Edition):

Birch, Noah Warren. “Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity.” 2013. Doctoral Dissertation, Loyola University Chicago. Accessed March 04, 2021. https://ecommons.luc.edu/luc_diss/504.

MLA Handbook (7^th Edition):

Birch, Noah Warren. “Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity.” 2013. Web. 04 Mar 2021.

Vancouver:

Birch NW. Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity. [Internet] [Doctoral dissertation]. Loyola University Chicago; 2013. [cited 2021 Mar 04]. Available from: https://ecommons.luc.edu/luc_diss/504.

Council of Science Editors:

Birch NW. Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity. [Doctoral Dissertation]. Loyola University Chicago; 2013. Available from: https://ecommons.luc.edu/luc_diss/504

McMaster University

7. Holzapfel, Nicholas. Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia.

Degree: PhD, 2016, McMaster University

URL: http://hdl.handle.net/11375/20628

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Musashi-2 (MSI2), a member of the Musashi family of RNA-binding proteins, is thought to play a critical role in the maintenance of stem cell populations… (more)

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Musashi-2 (MSI2), a member of the Musashi family of RNA-binding proteins, is thought to play a critical role in the maintenance of stem cell populations and in the formation of aggressive tumours. Multiple studies indicate that MSI2 plays an important role in the maintenance of hematopoietic stem cell (HSC) populations and recent studies in humans identify MSI2 as an independent prognostic factor for overall survival in patients with Acute Myeloid Leukemia (AML). Importantly, though correlative studies implicate MSI2 as a contributor to aggressive disease in human AML, no study to date has attempted to analyze the functional role of MSI2 in primary human AML samples. Furthermore, though MSI2 is critical for the maintenance of HSCs, the mechanisms through which MSI2 functions are unknown. The work presented in this thesis elucidates the biochemical mechanisms through which MSI2 functions and examines the functional role of MSI2 in human AML. Using a lentiviral-mediated shRNA knockdown of MSI2, I demonstrate that MSI2 is critical for the maintenance of human AML. A loss of MSI2 greatly impairs the ability of AML samples to maintain disease in a xenotransplantation assay. MSI2 is an RNA binding protein that is thought to repress the translation of target mRNAs in the cytoplasm and prevent the maturation of microRNAs (miRNAs) in the nucleus. The targets of MSI2 are believed to be potent regulators of stem-ness and dysregulation of these targets could very well contribute to neoplastic transformation. Cross-linking immunoprecipitation followed by next generation sequencing (CLIP-Seq), revealed the RNA binding properties of MSI2 and the RNA targets bound by MSI2. To identify novel MSI2 protein interactors, the MSI2 locus was endogenously tagged with the promiscuous biotin ligase BirA* and subjected to BioID analysis. When compared to appropriate controls, we were able to robustly identify proteins that associate with MSI2. The analysis of one of these protein binding partners, Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) reveals a critical role in the normal function of HSCs.

Thesis

Doctor of Philosophy (PhD)

The hematopoietic system is responsible for the production of billions of mature cells everyday. These mature cells are “differentiated”, meaning that they have gone through a process that has allowed them to become specialized to perform a very specific role. Throughout the process of differentiation, most functional cells lose their ability to proliferate. The continued production of these functional cells comes from a pool of rare, quiescent, hematopoietic stem cells (HSC). These cells maintain the production of mature cells throughout the lifetime of an organism. The Musashi-2 (MSI2) protein has been identified as a protein that is critical for the normal function of HSCs. By altering the levels of the MSI2, it is possible to greatly impair or enhance the activity of HSCs. Moreover, correlative studies implicate MSI2 as a contributor to aggressive Acute Myeloid Leukemia (AML), a…

Advisors/Committee Members: Hope, Kritstin, Biochemistry.

Subjects/Keywords: RNA-Binding Protein; Musashi; Hematopoiesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Holzapfel, N. (2016). Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/20628

Chicago Manual of Style (16^th Edition):

Holzapfel, Nicholas. “Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia.” 2016. Doctoral Dissertation, McMaster University. Accessed March 04, 2021. http://hdl.handle.net/11375/20628.

MLA Handbook (7^th Edition):

Holzapfel, Nicholas. “Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia.” 2016. Web. 04 Mar 2021.

Vancouver:

Holzapfel N. Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/11375/20628.

Council of Science Editors:

Holzapfel N. Investigating the Role of the RNA-Binding Protein MUSASHI-2 (MSI2) in Normal Hematopoiesis and Leukemia. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/20628

University of Toronto

8. Luca, Alice Maria. Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model.

Degree: 2015, University of Toronto

URL: http://hdl.handle.net/1807/70490

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Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disease, with 90% of SDS patients carrying a mutation in the SBDS gene. Due to limited… (more)

Subjects/Keywords: hematopoiesis; iPSCs; shwachman; 0758

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APA (6^th Edition):

Luca, A. M. (2015). Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/70490

Chicago Manual of Style (16^th Edition):

Luca, Alice Maria. “Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model.” 2015. Masters Thesis, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/70490.

MLA Handbook (7^th Edition):

Luca, Alice Maria. “Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model.” 2015. Web. 04 Mar 2021.

Vancouver:

Luca AM. Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/70490.

Council of Science Editors:

Luca AM. Regulation of Hematopoietic Progenitor Formation in a Shwachman Diamond Syndrome Induced Pluripotent Stem Cell Disease Model. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/70490

University of Ottawa

9. Rothberg, Janet L. Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis .

Degree: 2016, University of Ottawa

URL: http://hdl.handle.net/10393/35323

► Polycomb proteins are epigenetic regulators that are critical in mediating gene repression at critical stages during development. Core and accessory proteins make up the Polycomb… (more)

Subjects/Keywords: polycomb; hematopoiesis; erythropoiesis; stem cells

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APA (6^th Edition):

Rothberg, J. L. (2016). Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/35323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rothberg, Janet L. “Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis .” 2016. Thesis, University of Ottawa. Accessed March 04, 2021. http://hdl.handle.net/10393/35323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rothberg, Janet L. “Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis .” 2016. Web. 04 Mar 2021.

Vancouver:

Rothberg JL. Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis . [Internet] [Thesis]. University of Ottawa; 2016. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10393/35323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rothberg JL. Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis . [Thesis]. University of Ottawa; 2016. Available from: http://hdl.handle.net/10393/35323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Washington

10. Duggan, Jeffrey Mitchell. BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development.

Degree: PhD, 2017, University of Washington

URL: http://hdl.handle.net/1773/38641

► Hematopoiesis governs the production of mature cells of the lymphoid, myeloid and erythroid lineages. This process occurs in the bone marrow of adult mammals, and… (more)

Subjects/Keywords: BCAP; hematopoiesis; Immunology; Immunology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Duggan, J. M. (2017). BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/38641

Chicago Manual of Style (16^th Edition):

Duggan, Jeffrey Mitchell. “BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development.” 2017. Doctoral Dissertation, University of Washington. Accessed March 04, 2021. http://hdl.handle.net/1773/38641.

MLA Handbook (7^th Edition):

Duggan, Jeffrey Mitchell. “BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development.” 2017. Web. 04 Mar 2021.

Vancouver:

Duggan JM. BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development. [Internet] [Doctoral dissertation]. University of Washington; 2017. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1773/38641.

Council of Science Editors:

Duggan JM. BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development. [Doctoral Dissertation]. University of Washington; 2017. Available from: http://hdl.handle.net/1773/38641

11. Palande, Karishma. Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia.

Degree: 2011, Erasmus University Medical Center

URL: http://hdl.handle.net/1765/32457

► textabstractThe word hematopoiesis is derived from the greek words, haima meaning blood and poiesis meaning to make. Hematopoiesis is a tightly regulated process which ensures… (more)

Subjects/Keywords: hematopoiesis; leukemia

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APA (6^th Edition):

Palande, K. (2011). Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/32457

Chicago Manual of Style (16^th Edition):

Palande, Karishma. “Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia.” 2011. Doctoral Dissertation, Erasmus University Medical Center. Accessed March 04, 2021. http://hdl.handle.net/1765/32457.

MLA Handbook (7^th Edition):

Palande, Karishma. “Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia.” 2011. Web. 04 Mar 2021.

Vancouver:

Palande K. Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2011. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1765/32457.

Council of Science Editors:

Palande K. Redox-Controlled Signaling in Normal Myeloid Cell Development and Leukemia. [Doctoral Dissertation]. Erasmus University Medical Center; 2011. Available from: http://hdl.handle.net/1765/32457

12. ANG HEATHER YIN-KUAN. DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS.

Degree: 2012, National University of Singapore

URL: http://scholarbank.nus.edu.sg/handle/10635/47634

Subjects/Keywords: Reprogramming; Hematopoiesis

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APA (6^th Edition):

YIN-KUAN, A. H. (2012). DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/47634

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

YIN-KUAN, ANG HEATHER. “DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS.” 2012. Thesis, National University of Singapore. Accessed March 04, 2021. http://scholarbank.nus.edu.sg/handle/10635/47634.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

YIN-KUAN, ANG HEATHER. “DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS.” 2012. Web. 04 Mar 2021.

Vancouver:

YIN-KUAN AH. DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS. [Internet] [Thesis]. National University of Singapore; 2012. [cited 2021 Mar 04]. Available from: http://scholarbank.nus.edu.sg/handle/10635/47634.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

YIN-KUAN AH. DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS. [Thesis]. National University of Singapore; 2012. Available from: http://scholarbank.nus.edu.sg/handle/10635/47634

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. XU JIN. Study of definitive hematopoiesis in zebrafish.

Degree: 2008, National University of Singapore

URL: https://scholarbank.nus.edu.sg/handle/10635/160971

Subjects/Keywords: zebrafish hematopoiesis

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APA (6^th Edition):

JIN, X. (2008). Study of definitive hematopoiesis in zebrafish. (Thesis). National University of Singapore. Retrieved from https://scholarbank.nus.edu.sg/handle/10635/160971

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

JIN, XU. “Study of definitive hematopoiesis in zebrafish.” 2008. Thesis, National University of Singapore. Accessed March 04, 2021. https://scholarbank.nus.edu.sg/handle/10635/160971.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

JIN, XU. “Study of definitive hematopoiesis in zebrafish.” 2008. Web. 04 Mar 2021.

Vancouver:

JIN X. Study of definitive hematopoiesis in zebrafish. [Internet] [Thesis]. National University of Singapore; 2008. [cited 2021 Mar 04]. Available from: https://scholarbank.nus.edu.sg/handle/10635/160971.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

JIN X. Study of definitive hematopoiesis in zebrafish. [Thesis]. National University of Singapore; 2008. Available from: https://scholarbank.nus.edu.sg/handle/10635/160971

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Notre Dame

14. Jessica Renee Stoller-Conrad. Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>.

Degree: Biological Sciences, 2012, University of Notre Dame

URL: https://curate.nd.edu/show/k6439z92b62

► Blood development, or hematopoiesis, is an evolutionarily conserved process that is essential to life in many organisms. The hematopoetic development of Drosophila melanogaster is… (more)

Subjects/Keywords: genetics; hematopoiesis; development; Drosophila

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APA (6^th Edition):

Stoller-Conrad, J. R. (2012). Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/k6439z92b62

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Stoller-Conrad, Jessica Renee. “Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>.” 2012. Thesis, University of Notre Dame. Accessed March 04, 2021. https://curate.nd.edu/show/k6439z92b62.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Stoller-Conrad, Jessica Renee. “Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>.” 2012. Web. 04 Mar 2021.

Vancouver:

Stoller-Conrad JR. Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>. [Internet] [Thesis]. University of Notre Dame; 2012. [cited 2021 Mar 04]. Available from: https://curate.nd.edu/show/k6439z92b62.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Stoller-Conrad JR. Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>. [Thesis]. University of Notre Dame; 2012. Available from: https://curate.nd.edu/show/k6439z92b62

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

15. Csaszar, Elizabeth. Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate.

Degree: 2013, University of Toronto

URL: http://hdl.handle.net/1807/70068

►

Umbilical cord blood (UCB) cells fill a clinical need for hematopoietic stem and progenitor cell (HSPC) transplantation, and the ex vivo expansion of these cells… (more)

▼

Umbilical cord blood (UCB) cells fill a clinical need for hematopoietic stem and progenitor cell (HSPC) transplantation, and the ex vivo expansion of these cells provides an approach to increase their clinical relevance. Ex vivo HSPC expansion has been limited by a poor understanding of the interplay between stem cell autonomous and feedback mediated regulators. We hypothesized that developing strategies to modulate the HSPC microenvironment would enable enhanced expansion of these cells and a greater insight into the underlying biologic mechanisms. We developed a system for the optimized delivery of the transcription factor HOXB4 to human hematopoietic culture and revealed new insights into the context-dependent potentials and limitations of HOXB4. We investigated approaches for the global reduction of inhibitory feedback signaling and developed a fed-batch system that minimizes endogenously produced factors to create a more supportive environment for HSPC self-renewal. This strategy led to an 11-fold expansion of long-term repopulating HSCs in a clinically relevant bioreactor, producing a novel system for ex vivo expansion and generating a platform to assess HSPC enhancing factors. By combining the fed-batch system with the Notch Delta-1 ligand (DL1), we identified a mechanism whereby DL1 initiated a conversion from IL-6 cis-signaling to trans-signaling, resulting in the modulation of mature cell population production. This demonstrated the impact of cell lineage skewing on microenvironment regulation and the expansion of HSPCs. This work demonstrates how cell-cell interactions and feedback mediated signaling are critical regulators of HSPCs and the manipulation of these regulators can be used both to engineer HSPC expansion processes and to identify novel mechanisms within the hematopoietic system. This provides an important step towards the development of robust methods for the ex vivo expansion of UCB-derived cells and the ultimate goal of achieving cures in hematologic disease.

PhD

Advisors/Committee Members: Zandstra, Peter, Chemical Engineering and Applied Chemistry.

Subjects/Keywords: Stem cell bioengineering; hematopoiesis; 0541

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Csaszar, E. (2013). Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/70068

Chicago Manual of Style (16^th Edition):

Csaszar, Elizabeth. “Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate.” 2013. Doctoral Dissertation, University of Toronto. Accessed March 04, 2021. http://hdl.handle.net/1807/70068.

MLA Handbook (7^th Edition):

Csaszar, Elizabeth. “Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate.” 2013. Web. 04 Mar 2021.

Vancouver:

Csaszar E. Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate. [Internet] [Doctoral dissertation]. University of Toronto; 2013. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1807/70068.

Council of Science Editors:

Csaszar E. Feedback-mediated Regulation of Human Hematopoietic Stem Cell Fate. [Doctoral Dissertation]. University of Toronto; 2013. Available from: http://hdl.handle.net/1807/70068

University of Melbourne

16. Ang, Chow Hiang. Role of Npm1 in normal hematopoiesis and acute myeloid leukemia.

Degree: 2016, University of Melbourne

URL: http://hdl.handle.net/11343/127394

► The NPM1 gene encodes a multifunctional protein that shuttles between nucleus and cytoplasm, and is involved in diverse cellular activities including both proliferation and growth… (more)

▼ The NPM1 gene encodes a multifunctional protein that shuttles between nucleus and cytoplasm, and is involved in diverse cellular activities including both proliferation and growth suppression of cells. Genetic alterations in NPM1 are frequently involved in hematological malignancies. The NPM1c+ mutations, which are point mutations in exon 12 of the gene, resulting in aberrant localization of the NPM protein from the nucleolus to the cytoplasm, are exclusively reported in acute myeloid leukemia (AML). Previous studies showed that constitutive homozygous deletion of Npm1 in mice causes embryonic lethality due to defects in organ development and primitive hematopoiesis. This thesis employed a tamoxifen-inducible Cre-mediated conditional Npm1 knockout mouse model to investigate aspects of the normal role of Npm1 in adult hematopoiesis and of wild-type NPM in the context of leukemia. I showed that homozygous deletion of Npm1 in adult mice resulted in altered numbers of hematopoietic stem and progenitor cells, depletion of mature lymphoid cells and erythroid cells, and predisposed the mice to development of MDS-like hematological changes. Npm1-deficient hematopoietic stem and progenitor cells failed to proliferate normally when cultured in vitro. By using transplantation assays, I further established that Npm1-deficient hematopoietic stem cells exhibited a significantly impaired functional capacity for regeneration of blood cells in ablated hosts. Gene expression analysis of Npm1-deficient stem and progenitor cells by RNA-sequencing revealed that activation of the p53 pathway is likely to contribute the perturbed hematopoiesis caused by deletion of Npm1. This finding was extended to investigate aspects of the significance of residual wild-type Npm1 in AML pathogenesis by using the conditional Npm1 mouse model in combination with retroviral NPM1c+ or mice harboring a constitutive Flt3-ITD mutation. I showed that unlike wild-type NPM1, expression of NPM1c+ could not revert nor influence molecular changes caused by homozygous deletion of endogenous Npm1 in hematopoietic progenitor cells, and that unlike heterozygosity of wild-type and mutant Npm1 alleles, homozygous loss of Npm1 did not promote rapid leukemogenesis when combined with the AML-associated Flt3-ITD mutation. These observations support a model in which retention of wild-type NPM activity is required in leukemia.

Subjects/Keywords: Npm1; hematopoiesis; acute myeloid leukemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ang, C. H. (2016). Role of Npm1 in normal hematopoiesis and acute myeloid leukemia. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/127394

Chicago Manual of Style (16^th Edition):

Ang, Chow Hiang. “Role of Npm1 in normal hematopoiesis and acute myeloid leukemia.” 2016. Doctoral Dissertation, University of Melbourne. Accessed March 04, 2021. http://hdl.handle.net/11343/127394.

MLA Handbook (7^th Edition):

Ang, Chow Hiang. “Role of Npm1 in normal hematopoiesis and acute myeloid leukemia.” 2016. Web. 04 Mar 2021.

Vancouver:

Ang CH. Role of Npm1 in normal hematopoiesis and acute myeloid leukemia. [Internet] [Doctoral dissertation]. University of Melbourne; 2016. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/11343/127394.

Council of Science Editors:

Ang CH. Role of Npm1 in normal hematopoiesis and acute myeloid leukemia. [Doctoral Dissertation]. University of Melbourne; 2016. Available from: http://hdl.handle.net/11343/127394

University of Southern California

17. Wey, Shiuan. The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis.

Degree: PhD, Genetic, Molecular and Cellular Biology, 2013, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7218

► The endoplasmic reticulum (ER) is an intracellular organelle for protein folding, lipid synthesis and Ca²⁺ storage. It is also responsible for the transportation for most… (more)

▼ The endoplasmic reticulum (ER) is an intracellular organelle for protein folding, lipid synthesis and Ca²⁺ storage. It is also responsible for the transportation for most of the secretory and transmembrane proteins. When the protein load exceeds the ER folding capacity, the ER undergoes stress and activates a set of signaling cascades that is termed the unfolded protein response (UPR). The multifunctional GRP78 is the major ER molecular chaperone with protein folding abilities and the master regulator of the UPR, and recently has been shown that a subfraction of it is localized on the cell surface acting as a co-receptor for various signaling pathway activation. ❧ Traditionally GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors, thus, its role in the development of hematologic malignancies remains to be determined. In this thesis, elevated GRP78 expression was detected in leukemic blasts of adult patients, leukemia cell lines and inversely correlates with time to relapse in childhood acute lymphocytic leukemia. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell (HSC) population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null bone marrow cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first demonstration that GRP78 is a critical effector of leukemia progression, at least in part through control of oncogenic AKT signaling. Furthermore, overexpression of GRP78 renders human leukemic cells more resistant to AraC-induced apoptosis whereas knockdown of GRP78 sensitizes them, suggesting GRP78 is a novel potent therapeutic target for leukemia. ❧ Hematopoietic stem cell (HSC) homeostasis in the adult bone marrow (BM) is regulated by both intrinsic gene expression and interactions with extrinsic factors in the microenvironment. GRP78 has been shown to be critical for the maintenance of cellular homeostasis and prevention of apoptosis. Homozygous knockout mice of GRP78 are embryonic lethal at E3.5, indicating GRP78 is essential for embryonic cell growth and pluripotent cell survival. However, this has not been investigated in adult hematopoietic stem cells. Here we generated a conditional knockout mouse model that acutely deletes GRP78 in the hematopoietic system. GRP78 deficiency results in a significant reduction of HSCs, progenitor and lymphoid cell populations yet an increase in myeloid lineage granulocytes and monocytes in cKO mice. The GRP78-null induced reduction of the HSC pool can be attributed to enhanced apoptosis. In agreement, GRP78 deficient BM cells exhibited activated UPR signaling in all three branches and induced expression of pro-apoptotic… Advisors/Committee Members: Lee, Amy S. (Committee Chair), Kahn, Michael (Committee Member), Shibata, Darryl K. (Committee Member).

Subjects/Keywords: GRP78; AKT; PTEN; leukemia; hematopoiesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wey, S. (2013). The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7218

Chicago Manual of Style (16^th Edition):

Wey, Shiuan. “The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis.” 2013. Doctoral Dissertation, University of Southern California. Accessed March 04, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7218.

MLA Handbook (7^th Edition):

Wey, Shiuan. “The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis.” 2013. Web. 04 Mar 2021.

Vancouver:

Wey S. The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis. [Internet] [Doctoral dissertation]. University of Southern California; 2013. [cited 2021 Mar 04]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7218.

Council of Science Editors:

Wey S. The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis. [Doctoral Dissertation]. University of Southern California; 2013. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7218

University of Hong Kong

18. Man, Ki-fong. The role of calreticulin (CALR) in vertebrate hematopoiesis.

Degree: 2016, University of Hong Kong

URL: http://hdl.handle.net/10722/237867

► Calreticulin (CALR) is a multi-functional protein mainly controlling protein folding and calcium homeostasis in endoplasmic reticulum (ER). Recently, recurrent mutations in CALR have been found… (more)

▼ Calreticulin (CALR) is a multi-functional protein mainly controlling protein folding and calcium homeostasis in endoplasmic reticulum (ER). Recently, recurrent mutations in CALR have been found in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients without Janus kinase 2 (JAK2) or thrombopoietin receptor (MPL) mutations. Previous studies have shown that mutant forms of CALR interacted with MPL to activate JAK2-STAT5 signaling pathway in myeloproliferative neoplasm (MPN). However, the functional role of CALR in normal hematopoiesis remains unknown. In this study, we made use of zebrafish model to examine the unknown roles of Calr in vertebrate hematopoiesis. A somatic calr loss-of-function zebrafish model was generated by co-injecting two TALEN pairs separately targeting calr exon 1 and exon 5. Western-blot confirmed the reduction of calr protein in whole embryos as well as adult kidney marrow cells. Somatic calr mutations significantly increased the expression of genes associated with myeloid lineages, including pu.1, l-plastin, mpo and mpeg1, while decreased the expression of c-myb (hematopoietic stem cells (HSCs)) and rag1 (lymphocytes) in definitive hematopoiesis as shown by whole mount in situ hybridization (WISH). The myeloid-proliferation phenotype also persisted in adult hematopoiesis as shown by the expansion of myeloid cells in whole kidney marrows (WKMs) examined by flow cytometry. Unlike CALR mutations in MPN, calr loss-of-function did not affect subcellular phospho-stat5 status in the expanded myeloid population, suggests that calr regulates normal definitive hematopoiesis through an alternative pathway. We initially knock-down calr with morpholino (MO), which resulted in decrease in differentiated primitive myeloid cells and increase in definitive HSCs as shown by WISH, and is opposite to the results observed in calr loss-of-function model by double TALEN injection. However, western blot showed that calr protein level increased unexpectedly in calr morphant which might explain the phenotypic discrepancy between calr morphants and somatic mutants. To model CALR mutations, TALEN was also used to introduce frame-shifting mutations in zebrafish calr exon 9. In particular, a 7-bp deletion mutant, which resulted in a basic C-terminal resembling human CALR type-I and II mutations was generated. Although low fertility and survival rate limited the number of 7-bp mutants available for analysis, two out of four heterozygous F2 7-bp mutants developed tumor-like tissue in the head with infiltration of blastlike hematopoietic cells during early adulthood. Also, the percentage of myeloid cells increased significantly in their kidney marrows. These leukemic and MPN-like phenotypes were not observed in wild-type siblings or 5-bp mutants (resulted in a truncated C-terminal), under-scored the pathological potential of the novel basic C-terminal. In summary, we demonstrated the previously unknown role of Calr in regulating vertebrate definitive hematopoiesis, in particular, myelopoiesis.…

Subjects/Keywords: Hematopoiesis; Calreticulin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Man, K. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/237867

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Man, Ki-fong. “The role of calreticulin (CALR) in vertebrate hematopoiesis.” 2016. Thesis, University of Hong Kong. Accessed March 04, 2021. http://hdl.handle.net/10722/237867.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Man, Ki-fong. “The role of calreticulin (CALR) in vertebrate hematopoiesis.” 2016. Web. 04 Mar 2021.

Vancouver:

Man K. The role of calreticulin (CALR) in vertebrate hematopoiesis. [Internet] [Thesis]. University of Hong Kong; 2016. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/10722/237867.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Man K. The role of calreticulin (CALR) in vertebrate hematopoiesis. [Thesis]. University of Hong Kong; 2016. Available from: http://hdl.handle.net/10722/237867

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of British Columbia

19. Hogge, Donna Eileen. Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors.

Degree: PhD, Pathology, 1987, University of British Columbia

URL: http://hdl.handle.net/2429/27316

► In most neoplasms malignant change occurs in a single cell which then proliferates. My purpose was to explore methods to study the cell that gives… (more)

▼ In most neoplasms malignant change occurs in a single cell which then proliferates. My purpose was to explore methods to study the cell that gives rise to hemopoietic cancer and to investigate the abnormalities at a molecular level. Cytogenetic analysis of cells from individual hemopoietic colonies revealed that monosomy 7 syndrome, a hematologic disorder of childhood, arises in a primitive cell capable of differentiating down both myeloid and erythroid pathways. Long-term bone marrow cultures (LTC) from patients with chronic myelogenous leukemia (CML) favor the growth of Philadelphia chromosome (Ph) negative progenitors which, although cytogenetically normal, could have been part of the malignant clone at a stage prior to the development of the Ph. LTC's were initiated with cells from 2 women with CML who were heterozygous for 2 electrophoretically distinct glucose-6-phosphate dehydrogenase (G6PD) enzyme variants. In one patient, 2/11 progenitors were Ph-negative after 4 to 6 weeks in LTC and 4/30 were nonclonal by G6PD enzyme analysis, i.e. the colonies expressed the enzyme not found in the malignant clone. In this case, karyotypically normal cells were truly normal. Next, gene transfer to human hemopoietic cells was demonstrated using recombinant retrovirus carrying the selectable marker gene, neor. With the K562 human leukemic cell line as targets up to 60% of infected cells became G418 resistant (G418r). Cloned populations of G418r cells showed unique patterns of retroviral integration in K562 DNA. When the target cells were progenitors from normal marrow, CML blood or fetal liver, the highest frequencies of G418r granulocyte-macrophage or large erythroid colonies was 16% and 5% respectively. Experiments infecting bone marrow cells in LTC with neor virus produced up to 2% G418r colonies after as long as 3 weeks in culture. Using v-src virus to infect LTC failed to perturb hemopoiesis, although infection of bone marrow-derived cells in these cultures was documented. In summary: 1. Unique populations of hemopoietic progenitors can be identified in culture using several genetic markers including chromosomes, G6PD analysis or gene transfer. 2. The feasibility of retroviral-mediated gene transfer for use on human hemopoietic cells has been demonstrated.

Subjects/Keywords: Transfection; Hematopoiesis

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APA (6^th Edition):

Hogge, D. E. (1987). Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors. (Doctoral Dissertation). University of British Columbia. Retrieved from http://hdl.handle.net/2429/27316

Chicago Manual of Style (16^th Edition):

Hogge, Donna Eileen. “Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors.” 1987. Doctoral Dissertation, University of British Columbia. Accessed March 04, 2021. http://hdl.handle.net/2429/27316.

MLA Handbook (7^th Edition):

Hogge, Donna Eileen. “Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors.” 1987. Web. 04 Mar 2021.

Vancouver:

Hogge DE. Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors. [Internet] [Doctoral dissertation]. University of British Columbia; 1987. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2429/27316.

Council of Science Editors:

Hogge DE. Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors. [Doctoral Dissertation]. University of British Columbia; 1987. Available from: http://hdl.handle.net/2429/27316

University of Rochester

20. Frame, Jenna M. Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac.

Degree: PhD, 2015, University of Rochester

URL: http://hdl.handle.net/1802/30111

► Hematopoietic stem cells are specified during embryogenesis from a specialized population of endothelium, termed hemogenic endothelium, which resides in major embryonic arteries and requires the… (more)

▼ Hematopoietic stem cells are specified during embryogenesis from a specialized population of endothelium, termed hemogenic endothelium, which resides in major embryonic arteries and requires the hematopoietic transcription factor Runx1. Despite the established presence of these functional hematopoietic stem cells in the midgestation mouse embryo, embryonic survival is dependent on the earlier emergence and differentiation of a transient wave of yolk sac-derived erythro-myeloid progenitors. Previously, our laboratory confirmed that erythro-myeloid progenitors preferentially emerge from murine embryonic stem cell cultures. Conversely, transplantable hematopoietic stem cells have not yet been derived from embryonic stem cells, indicating the need to better understand the regulation of hematopoietic potential during development. Here, we define the cellular origin of erythro-myeloid progenitors, and begin to address mechanisms regulating their specification of during embryogenesis. We confirmed reports that erythro-myeloid progenitors require Runx1 for formation, and immunohistochemical studies strongly suggest they are derived from hemogenic endothelium. Subsequently, we examined hematopoietic emergence in Runx1+/- yolk sacs, which had reported alterations in hematopoietic potential, and found that reduced Runx1 dosage both delays the emergence of erythro-myeloid potential from hemogenic endothelium and results in increased proliferative potential. In the aorta, the specification of hematopoietic stem cell-producing hemogenic endothelium is dependent on embryonic circulation and β-catenin signaling. Interestingly, in the yolk sac, we found that hemogenic endothelium does not appear to be restricted to arterial vasculature, and analysis of circulation-deficient yolk sacs revealed normal cluster morphology and location, indicating the endothelial-tohematopoietic transition can occur in vivo without blood flow. Conversely, however, exogenous activation of β-catenin signaling in whole yolk sacs increased hematopoietic colony-forming activity. Subsequent in vitro assays and analysis of β-catenin reporter yolk sacs implicate a role for β-catenin signaling in hemogenic endothelium. Therefore, while emergence of erythro-myeloid progenitors from hemogenic endothelium is not dependent on blood flow or arterial identity, β-catenin appears to play a common role in hematopoietic specification from endothelium. Together, these data indicate the presence of heterogeneous populations of hemogenic endothelia in the mammalian conceptus, and highlight the need to understand developmental cues that influence the hematopoietic potential of each population in order to efficiently derive them in vitro.

Subjects/Keywords: Hematopoiesis; Fetal Hematopoiesis; Runx1; Embryogenesis; Erythro-Myeloid Progenitors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Frame, J. M. (2015). Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/30111

Chicago Manual of Style (16^th Edition):

Frame, Jenna M. “Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac.” 2015. Doctoral Dissertation, University of Rochester. Accessed March 04, 2021. http://hdl.handle.net/1802/30111.

MLA Handbook (7^th Edition):

Frame, Jenna M. “Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac.” 2015. Web. 04 Mar 2021.

Vancouver:

Frame JM. Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/1802/30111.

Council of Science Editors:

Frame JM. Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac. [Doctoral Dissertation]. University of Rochester; 2015. Available from: http://hdl.handle.net/1802/30111

University of Oxford

21. Buchrieser, Julian. Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs).

Degree: PhD, 2016, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730166

► Tissue-resident macrophages (MΦ) such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells… (more)

▼ Tissue-resident macrophages (MΦ) such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident MΦ self-renew locally, independently of circulating adult monocytes and HSCs. In contrast, adult blood monocytes as well as infiltrating, gut and dermal MΦ derive from Myb-dependent HSCs and are less proliferative. These findings are derived from the mouse, using gene knock-outs and lineage tracing, but their applicability to human development has not been formally demonstrated. Here I use a human pluripotent stem cell (hPSC) differentiation model of hematopoiesis, capable of monocyte/MΦ production over prolonged periods of time, as a tool to investigate human mononuclear phagocyte ontogeny. Using a transcriptomic approach I showed that hiPSC-derived monocytes/MΦ (iPS-Mo/MΦ) produced early in differentiation (first weeks) are more proliferative and less immunologically mature than iPS-Mo/MΦ produced at a later time point. I therefore hypothesised either that iPS-Mo/MΦ only become fully mature after several weeks of differentiation or that there are two developmentally distinct waves of MΦ produced over time. By comparing the transcription profile of iPS-Mo/MΦs to that of primary adult blood monocytes and fetal microglia I then showed that early and late iPS-Mo/MΦs were transcriptionally closer to fetal microglia than to adult blood monocytes. To further investigate if iPS-Mo/MΦs are indeed of the same developmental origin as MYB-independent MΦ such as microglia, I used a CRISPR-Cas9 knock-out strategy to show for the first time, that human iPS-Mo/MΦs develop in a MYB-independent, RUNX1 and SPI1 (PU.1)-dependent fashion. This result makes human iPS-Mo/MΦs developmentally related to, and a good model for, MYB-independent tissue-resident \Macros such as alveolar and kidney MΦs, microglia, Kupffer and Langerhans cells. Interestingly, while MYB was not required for the generation of iPS-Mo/MΦs, its knock-out resulted in an increase in iPS-Mo/MΦ production. To investigate this increase I developed two methods for quantifying the differentiation bottleneck occurring during hiPSC differentiation to iPS-Mo/MΦs. Those techniques highlighted a potential increase in progenitor cell generation in MYB KO cells and thus lay foundation to improve our technical understanding of EB differentiation and will enable enhanced manipulation of the EB model.

Subjects/Keywords: 612.4; Hematopoiesis; Primitive hematopoiesis; Macrophage; MYB; SPI1; RUNX1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Buchrieser, J. (2016). Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs). (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730166

Chicago Manual of Style (16^th Edition):

Buchrieser, Julian. “Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs).” 2016. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021. http://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730166.

MLA Handbook (7^th Edition):

Buchrieser, Julian. “Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs).” 2016. Web. 04 Mar 2021.

Vancouver:

Buchrieser J. Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs). [Internet] [Doctoral dissertation]. University of Oxford; 2016. [cited 2021 Mar 04]. Available from: http://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730166.

Council of Science Editors:

Buchrieser J. Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs). [Doctoral Dissertation]. University of Oxford; 2016. Available from: http://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730166

University of Alberta

22. Pillay, Laura M. Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis.

Degree: PhD, Department of Biological Sciences, 2015, University of Alberta

URL: https://era.library.ualberta.ca/files/dz010s67m

► Improper regulation of hematopoiesis generates a spectrum of defects that range from anemia and embryonic lethality to leukemia. Identifying the molecular pathways that regulate hematopoiesis… (more)

▼ Improper regulation of hematopoiesis generates a spectrum of defects that range from anemia and embryonic lethality to leukemia. Identifying the molecular pathways that regulate hematopoiesis is therefore a major goal of both basic and clinical biology. Vertebrate hematopoiesis occurs in two embryonic waves. The first wave, primitive hematopoiesis, influences the morphology of the developing embryonic circulatory system and produces circulating erythrocytes that facilitate tissue oxygenation during periods of rapid embryonic growth. The second, definitive wave of hematopoiesis produces multipotent hematopoietic stem cells (HSCs) that are able to differentiate into all mature blood cell lineages, self-renew, and maintain adult hematopoiesis for life. A major challenge in developmental hematopoiesis is to determine the molecular cues that regulate each phase of hematopoiesis. Previous analyses using vertebrate models have identified molecular pathways that govern both primitive and definitive hematopoiesis. These pathways are conserved among vertebrates, and the critical mammalian hematopoietic genes have clear orthologues in zebrafish. Using zebrafish as a model organism, we have identified essential regulators of both primitive and definitive hematopoiesis. We have defined a critical role for the homeodomain transcription factors Meis1 and Pbx in regulating primitive erythropoiesis. Inhibiting zebrafish Meis1 and Pbx protein synthesis cripples the production of circulating erythrocytes, and generates defects in erythropoietic gene expression. Our data place Meis1 and Pbx upstream of gata1 in the erythropoietic transcription factor hierarchy. We have also elucidated a novel role for retinoic acid (RA) signaling in definitive hematopoiesis, as RA-depleted embryos fail to produce HSCs. Previous studies have implicated RA as a critical regulator of murine Notch1 signaling, and suggest that endothelial cells require RA in order to adopt a hemogenic fate. However, our research suggests that RA is required for HSC formation prior to the formation of dorsal aorta hemogenic endothelium and that, unlike in mice, zebrafish RA does not regulate HSC formation through the Notch1-signaling pathway. Previous research by our lab has implicated the homeodomain transcription factor Hmx4 as a critical regulator of zebrafish forebrain and ocular development, and has shown that Hmx4 modulates RA signaling. However, prior to this work, the contribution of Hmx4 to embryonic hematopoiesis was unknown. We have identified putative RA-independent and dependent roles for Hmx4 in regulating primitive and definitive hematopoiesis, respectively.

Subjects/Keywords: Primitive Hematopoiesis; Hmx4; Homeodomain Transcription Factors; Hematopoiesis; Sharkey; Definitive Hematopoiesis; Meis1; Zinc Finger Nuclease; Retinoic Acid; Zebrafish; Pbx; TALEN

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APA (6^th Edition):

Pillay, L. M. (2015). Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/dz010s67m

Chicago Manual of Style (16^th Edition):

Pillay, Laura M. “Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis.” 2015. Doctoral Dissertation, University of Alberta. Accessed March 04, 2021. https://era.library.ualberta.ca/files/dz010s67m.

MLA Handbook (7^th Edition):

Pillay, Laura M. “Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis.” 2015. Web. 04 Mar 2021.

Vancouver:

Pillay LM. Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis. [Internet] [Doctoral dissertation]. University of Alberta; 2015. [cited 2021 Mar 04]. Available from: https://era.library.ualberta.ca/files/dz010s67m.

Council of Science Editors:

Pillay LM. Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis. [Doctoral Dissertation]. University of Alberta; 2015. Available from: https://era.library.ualberta.ca/files/dz010s67m

Harvard University

23. Netravali, Ilka Arun. Elucidation of plasmacytoid dendritic cell development.

Degree: PhD, Biology: Medical Sciences, Division of, 2014, Harvard University

URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274587

► Most currently defined hematopoietic progenitor pools are heterogeneous, contributing to uncertainty regarding the development of certain blood cells. The origins of plasmacytoid dendritic cells, for… (more)

Subjects/Keywords: Immunology; hematopoiesis; plasmacytoid dendritic cell; sialic acid

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APA (6^th Edition):

Netravali, I. A. (2014). Elucidation of plasmacytoid dendritic cell development. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274587

Chicago Manual of Style (16^th Edition):

Netravali, Ilka Arun. “Elucidation of plasmacytoid dendritic cell development.” 2014. Doctoral Dissertation, Harvard University. Accessed March 04, 2021. http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274587.

MLA Handbook (7^th Edition):

Netravali, Ilka Arun. “Elucidation of plasmacytoid dendritic cell development.” 2014. Web. 04 Mar 2021.

Vancouver:

Netravali IA. Elucidation of plasmacytoid dendritic cell development. [Internet] [Doctoral dissertation]. Harvard University; 2014. [cited 2021 Mar 04]. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274587.

Council of Science Editors:

Netravali IA. Elucidation of plasmacytoid dendritic cell development. [Doctoral Dissertation]. Harvard University; 2014. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274587

Northeastern University

24. Peters, Michael J. Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish.

Degree: PhD, Department of Marine and Environmental Sciences, 2018, Northeastern University

URL: http://hdl.handle.net/2047/D20293303

► The Antarctic icefishes (Channichthyidae) are the only vertebrate taxon whose species do not produce red blood cells, thereby providing a natural mutant model to study… (more)

Subjects/Keywords: anemia; CRISPR; erythropoiesis; gene editing; hematopoiesis; zebrafish

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APA (6^th Edition):

Peters, M. J. (2018). Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish. (Doctoral Dissertation). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20293303

Chicago Manual of Style (16^th Edition):

Peters, Michael J. “Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish.” 2018. Doctoral Dissertation, Northeastern University. Accessed March 04, 2021. http://hdl.handle.net/2047/D20293303.

MLA Handbook (7^th Edition):

Peters, Michael J. “Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish.” 2018. Web. 04 Mar 2021.

Vancouver:

Peters MJ. Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish. [Internet] [Doctoral dissertation]. Northeastern University; 2018. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2047/D20293303.

Council of Science Editors:

Peters MJ. Modeling the evolutionary loss of erythroid genes by Antarctic icefishes: analysis of the hemogen gene using transgenic and mutant zebrafish. [Doctoral Dissertation]. Northeastern University; 2018. Available from: http://hdl.handle.net/2047/D20293303

Boston University

25. Dharampuriya, Priyanka. Role of epigenetics in hematopoietic stem cell development.

Degree: MS, Medical Sciences, 2017, Boston University

URL: http://hdl.handle.net/2144/23717

► In 2106, there were 171,550 new cases of blood cancers and over one million people in the United States living with one of these disorders.… (more)

▼ In 2106, there were 171,550 new cases of blood cancers and over one million people in the United States living with one of these disorders. Bone marrow transplants have good outcomes, but these procedures require a donor who is a perfect match, and thus many patients are unable to receive treatment. It is important to find patient-derived treatments, such as molecules which stimulate hematopoietic stem cell (HSC) formation without the need for a donor. Therefore, a study was initiated to use human-induced pluripotent stem cell (hiPSC) technology to make a patient-derived, personalized HSC. Epigenetic regulators are divided into readers, writers, and erasers, and each of these classes has shown some effect on HSC formation. Writers add functional groups to deoxyribonucleic acid (DNA) and histone proteins, whereas erasers remove them. Readers are groups on transcription factors which interpret these changes and increase or decrease the recruitment of transcriptional machinery accordingly. In this study, a screen of 12 different candidate molecules with distinct epigenetic targets in casper zebrafish was conducted at 36 hours postfertilization (hpf) to reveal increases or decreases in definitive HSC development. The two writer molecules, C646 (histone acetyltransferase, or HAT, inhibitor) and OICR9249 (WDR5 inhibitor), and the two eraser molecules, Ex-527 (Sirt1 inhibitor) and JIB-04 (bromodomain inhibitor), showed varying degrees of increasing HSC formation. Of these molecules, C646 created the most significant increase and was further tested in the zebrafish at 48 and 72 hpf and in a murine model using ex vivo technique and a colony-forming unit (CFU) assay. In contrast to these results, the two eraser molecules, entinostat (class I histone deacetylase, or HDAC, inhibitor) and vorinostat (general HDAC inhibitor), were found to decrease HSC formation in zebrafish. The overall findings of this study provide insight into specific epigenetic regulators in HSC development and identify particular epigenetic markers that could regulate HSC formation from endothelial cells. This discovery will be a stepping stone in utilizing patient-derived hemogenic endothelial cells as a novel source of bone marrow-independent HSCs to treat patients with leukemia, lymphoma, and bone marrow cancers.

Subjects/Keywords: Medicine; HDAC; Epigenetics; Hematopoiesis; Histone acetyltransferase

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APA (6^th Edition):

Dharampuriya, P. (2017). Role of epigenetics in hematopoietic stem cell development. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/23717

Chicago Manual of Style (16^th Edition):

Dharampuriya, Priyanka. “Role of epigenetics in hematopoietic stem cell development.” 2017. Masters Thesis, Boston University. Accessed March 04, 2021. http://hdl.handle.net/2144/23717.

MLA Handbook (7^th Edition):

Dharampuriya, Priyanka. “Role of epigenetics in hematopoietic stem cell development.” 2017. Web. 04 Mar 2021.

Vancouver:

Dharampuriya P. Role of epigenetics in hematopoietic stem cell development. [Internet] [Masters thesis]. Boston University; 2017. [cited 2021 Mar 04]. Available from: http://hdl.handle.net/2144/23717.

Council of Science Editors:

Dharampuriya P. Role of epigenetics in hematopoietic stem cell development. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/23717

Columbia University

26. Corrigan, David Joseph. Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis.

Degree: 2018, Columbia University

URL: https://doi.org/10.7916/D8S19K1D

► PRDM16 is a transcriptional co-regulator that is highly expressed in HSCs and required for their maintenance. It is also involved in translocations in acute myeloid… (more)

▼ PRDM16 is a transcriptional co-regulator that is highly expressed in HSCs and required for their maintenance. It is also involved in translocations in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and T-cell acute lymphoblastic leukemia. Prdm16 is expressed as both full-length (f Prdm16) and short-length (s-Prdm16) isoforms, the latter lacking an N-terminal PR domain homologous to SET methyltransferase domains. The roles of both isoforms in normal and malignant hematopoiesis are unclear. In chromosomal rearrangements involving PRDM16, the PR domain is deleted. Furthermore, overexpression of s-Prdm16, but not f-Prdm16, can cause leukemia in a p53-/- background predisposed to malignancy. Based on this, s-Prdm16 has been proposed as an oncogene whereas f-Prdm16 has been suggested to possess tumor suppressor activity. The aim of this thesis was to more clearly elucidate the role of each Prdm16 isoform in normal and malignant hematopoiesis. We first showed that Prdm16 is essential for adult HSC maintenance using a conditional deletion mouse model specific for hematopoietic cells, as previous findings using an embryonic-lethal global Prdm16-/- mouse demonstrated this only in fetal liver. We then found, using a specific f-Prdm16-/- mouse model, that full-length Prdm16 is essential for HSC maintenance and induces multiple genes involved in GTPase signaling and represses inflammation. Based on a comparison of Prdm16-/- HSCs lacking both isoforms, and f-Prdm16-/- HSCs which express s-Prdm16, we were able to infer some hematopoietic properties of s-Prdm16 – namely that this isoform induces inflammatory gene expression and supports development of a Lineage-Sca1+cKit- lymphoid progenitor distinct from CLPs which predominantly differentiates into marginal zone B cells. s-Prdm16 expression alone, however, was not sufficient to maintain HSCs. We used a mouse model of human MLL-AF9 leukemia and found that leukemia derived from Prdm16-deficient HSCs had extended latency, although expression of Prdm16 decreases during MLL-AF9 transformation and is undetectable in ex vivo leukemic cells. Forced expression of f-Prdm16 in these cells further extended leukemic latency, while forced expression of s-Prdm16 shortened latency. Gene expression profiling using RNAseq indicated that forced expression of f-Prdm16 resulted in altered respiratory metabolism of MLL-AF9 cells, whereas expression of s-Prdm16 induced a strong inflammatory gene signature, comparable to that seen in HSCs expressing only s-Prdm16. Several inflammatory cytokines and chemokines induced by s-Prdm16 are associated with MDS and with a worse prognosis in human AML. Furthermore, leukemia expressing s-Prdm16 had an elevated number of cells with abnormal nuclei, characteristic of dysplasia. Finally, we performed an analysis of PRDM16 in human AML from the publically-available Cancer Genome Atlas dataset, containing clinical and gene expression data for 179 cases of AML. PRDM16 expression negatively correlated with overall survival, both in the…

Subjects/Keywords: Immunology; Microbiology; Hematopoiesis; Genetic transcription – Regulation; Proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Corrigan, D. J. (2018). Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8S19K1D

Chicago Manual of Style (16^th Edition):

Corrigan, David Joseph. “Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis.” 2018. Doctoral Dissertation, Columbia University. Accessed March 04, 2021. https://doi.org/10.7916/D8S19K1D.

MLA Handbook (7^th Edition):

Corrigan, David Joseph. “Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis.” 2018. Web. 04 Mar 2021.

Vancouver:

Corrigan DJ. Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Mar 04]. Available from: https://doi.org/10.7916/D8S19K1D.

Council of Science Editors:

Corrigan DJ. Differential Roles of PRDM16 Isoforms in Normal and Malignant Hematopoiesis. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8S19K1D

Columbia University

27. Mumau, Melanie. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.

Degree: 2018, Columbia University

URL: https://doi.org/10.7916/D8WD5BGJ

► The decisions stem cells make impact both the development of adult vertebrates and systems within the body that require cellular replenishment to sustain life. Regardless… (more)

▼ The decisions stem cells make impact both the development of adult vertebrates and systems within the body that require cellular replenishment to sustain life. Regardless whether a stem cell remains quiescent, divides, differentiates, or undergoes apoptosis—these processes are precisely controlled by internal gene regulatory networks that are instructed by external stimuli. The exact mechanisms governing stem cell fate are not completely understood. These studies explore new ways in which cell fate is mediated. Through a study of mitochondrial content in human embryonic stem cells (hESCs) and their differentiated progeny, we discovered differences in mitochondrial morphologies. Mitochondria began as elongated and networked structures in self-renewing conditions and changed their shape after differentiation. The addition of external growth factors that direct hESCs toward the definitive endoderm (DE) lineage promoted mitochondrial fragmentation, which was mediated by the mitochondrial fission machinery. Globular, punctate mitochondria were observed prior to the induction of the DE-specific transcriptional program. Differentiation of hESCs to other lineages did not result in any mitochondrial shape changes. Thus, mitochondrial fission in differentiating hESCs, an internal cellular process, is induced by DE-inducing external stimuli, an effect that was lineage specific. In a second study, we investigated the role of the splenic environment in the development of the blood system—during hematopoiesis. The spleen made a distinct contribution to hematopoiesis, a process predominantly attributed to the bone marrow. We discovered a previously unidentified population of cells, uniquely represented in the mouse spleen that could develop into erythrocytes, monocytes, granulocytes, and platelets. These multipotent progenitors of the spleen (MPPS) expressed higher levels of the transcription factor, NR4A1 compared to their bone marrow counterparts and relied on NR4A1 expression to direct their cell fate. The activation of NR4A1 in MPPS biased their production of monocytes and granulocytes in vitro whereas NR4A1-deficient MPPS over-produced erythroid lineage cells in vivo. Together, these data suggest the splenic niche supports distinct myeloid differentiation programs of multi-lineage progenitors cells. Both studies identify new mechanisms by which external stimuli regulate internal mechanisms of cell fate. These insights provide a better understanding of stem and progenitor cell differentiation that have the potential to impact cellular replacement therapies.

Subjects/Keywords: Immunology; Hematopoiesis; Embryonic stem cells; Cytology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mumau, M. (2018). The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8WD5BGJ

Chicago Manual of Style (16^th Edition):

Mumau, Melanie. “The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.” 2018. Doctoral Dissertation, Columbia University. Accessed March 04, 2021. https://doi.org/10.7916/D8WD5BGJ.

MLA Handbook (7^th Edition):

Mumau, Melanie. “The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis.” 2018. Web. 04 Mar 2021.

Vancouver:

Mumau M. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Mar 04]. Available from: https://doi.org/10.7916/D8WD5BGJ.

Council of Science Editors:

Mumau M. The ins and outs of stem cells: regulation of cell fate in embryonic stem cells and hematopoiesis. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8WD5BGJ

University of Oxford

28. Bonkhofer, Florian. Identification of novel Runx1 targets involved in HSC development.

Degree: PhD, 2017, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740861

► Haematopoietic stem and progenitor cells (HSPCs) are de novo generated within in the ventral aspects of the embryonic dorsal aorta (DA). Cells of this haemogenic… (more)

Subjects/Keywords: 610; Medical sciences – Research; Runx1; Hematopoiesis

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APA (6^th Edition):

Bonkhofer, F. (2017). Identification of novel Runx1 targets involved in HSC development. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740861

Chicago Manual of Style (16^th Edition):

Bonkhofer, Florian. “Identification of novel Runx1 targets involved in HSC development.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021. http://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740861.

MLA Handbook (7^th Edition):

Bonkhofer, Florian. “Identification of novel Runx1 targets involved in HSC development.” 2017. Web. 04 Mar 2021.

Vancouver:

Bonkhofer F. Identification of novel Runx1 targets involved in HSC development. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04]. Available from: http://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740861.

Council of Science Editors:

Bonkhofer F. Identification of novel Runx1 targets involved in HSC development. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:4badf9f4-f796-4063-8176-dd57644fd811 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740861

Hong Kong University of Science and Technology

29. Wu, Yi. Establishment of a genetic system for myeloid cell fate mapping in zebrafish.

Degree: 2014, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-86325 ; https://doi.org/10.14711/thesis-b1334218 ; http://repository.ust.hk/ir/bitstream/1783.1-86325/1/th_redirect.html

► Myeloid cells, composed of granulocytes and monocytes, have very significant roles in the immune response and tissue remodeling. All myeloid cells are derived from hematopoiesis.… (more)

▼ Myeloid cells, composed of granulocytes and monocytes, have very significant roles in the immune response and tissue remodeling. All myeloid cells are derived from hematopoiesis. Similar to mammals, zebrafish hematopoiesis consists of two waves, primitive hematopoiesis and definitive hematopoiesis. These two waves take place in different locations at different time course. Primitive hematopoiesis is a transient wave and takes place in the early stage. It mainly gives rise to myeloid cells and erythrocytes. Definitive hematopoiesis can generate hematopoietic stem cells, which can give rise to all kinds of cells of blood lineage including myeloid cells, erythrocytes and lymphocytes. The macrophages generated by hematopoiesis will migrate into different organs to become tissue resident macrophages, such as microglia in the brain. The origin of tissue resident macrophages is an interesting research field to investigate. Myeloid cell fate mapping in mice has been conducted by many groups to figure out which hematopoietic wave tissue resident macrophages are derived from. However, there has not been a consensus in this issue yet, and it still remains an open question. We tried to label different waves of myeloid cells in zebrafish embryos and observe their distribution in the adult organs. Two transgenic lines Tg(coro1a:CreER ^T2) and Tg(coro1a:LOXP-DsRedx-LOXP-eGFP) were generated, and this Cre-lopx system can permanently convert Dsred positive myeloid cells into GFP positive myeloid cells. Taking the advantage of model system zebrafish, we can label one wave of myeloid cells with different methods. Preliminary data show that controlling the time of labelling using Tg(coro1a:CreER ^T2) line or controlling the location of labelling using (hsp70:mCherry-T2a-CreER^T2) ^#12 line with a local IR laser induction may effectively label myeloid cells at different time course or in different locations. Therefore, it is shown this system can be applied in the myeloid cell fate mapping experiment in zebrafish.

Subjects/Keywords: Hematopoiesis ; Zebra danio ; Genetics ; Stem cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wu, Y. (2014). Establishment of a genetic system for myeloid cell fate mapping in zebrafish. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-86325 ; https://doi.org/10.14711/thesis-b1334218 ; http://repository.ust.hk/ir/bitstream/1783.1-86325/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wu, Yi. “Establishment of a genetic system for myeloid cell fate mapping in zebrafish.” 2014. Thesis, Hong Kong University of Science and Technology. Accessed March 04, 2021. http://repository.ust.hk/ir/Record/1783.1-86325 ; https://doi.org/10.14711/thesis-b1334218 ; http://repository.ust.hk/ir/bitstream/1783.1-86325/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wu, Yi. “Establishment of a genetic system for myeloid cell fate mapping in zebrafish.” 2014. Web. 04 Mar 2021.

Vancouver:

Wu Y. Establishment of a genetic system for myeloid cell fate mapping in zebrafish. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2014. [cited 2021 Mar 04]. Available from: http://repository.ust.hk/ir/Record/1783.1-86325 ; https://doi.org/10.14711/thesis-b1334218 ; http://repository.ust.hk/ir/bitstream/1783.1-86325/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wu Y. Establishment of a genetic system for myeloid cell fate mapping in zebrafish. [Thesis]. Hong Kong University of Science and Technology; 2014. Available from: http://repository.ust.hk/ir/Record/1783.1-86325 ; https://doi.org/10.14711/thesis-b1334218 ; http://repository.ust.hk/ir/bitstream/1783.1-86325/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Notre Dame

30. Dawn Weseli Hopkins. The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>.

Degree: Biological Sciences, 2014, University of Notre Dame

URL: https://curate.nd.edu/show/ng451g07s8m

► Drosophila has emerged as an important model system in the examination of the hematopoietic process owing to the conserved nature of many of the… (more)

▼ Drosophila has emerged as an important model system in the examination of the hematopoietic process owing to the conserved nature of many of the transcription factors and signaling pathways utilized to produce blood cells. Mirroring vertebrate hematopoiesis, Drosophila generate hemocytes in a distinct spatial temporal course. The focus of the following study concerns the definitive wave of hematopoiesis, which occurs in the lymph gland (LG). Through microarray analysis, bag-of-marbles (bam) was found to be transcriptionally active in the LG. Furthermore, Bam was expressed in both the niche cells of the posterior signaling center (PSC) and the progenitors of the medullary zone (MZ). The progenitor cells of bam mutant LGs prematurely differentiate into all three hemocyte types. Additionally, the PSC number is dramatically increased and the cells are dispersed throughout the primary LG tissue. These two distinct phenotypes demonstrate that bam has cell-autonomous functions in these separate regions of the LG. In order to further define the function of bam, a sensitized third chromosome deficiency screen was conducted implementing one null copy of bam (bam∆86) and the lamellocyte specific enhancer reporter, MSNF9mcherry. Through continued screening, two genes were uncovered that displayed a bam-dependent lamellocyte suppression, Rab11 and qin. An additional three genes previously unknown to function in hematopoiesis were found to suppress lamellocyte differentiation in a bam-independent manner (msps, cct1, and ChaVAchT). Further investigation of the interaction between Bam and Qin revealed co-localization of the two proteins in early third instar LGs and a significant reduction of hematopoietic progenitors in LGs heterozygous for both bam∆86 and qine03728. Forced expression of the C-terminal domain of qin with a MZ-specific driver caused significant expansion of the MZ, similar to the full-length construct and was able to rescue the reduced LG and MZ size characteristic of qin mutants, highlighting the importance of the Tudor domains located in this fragment. Lastly, qin and bam may be functioning through an epigenetic mechanism as the nuclear localization of HP1a (Heterochromatin protein 1a) is altered in heterozygous mutant LGs. Together, these findings have provided important insights into the genetic control of hematopoietic progenitor fate in Drosophila. Advisors/Committee Members: Dr. Kevin Vaughan, Committee Member, Dr. Robert Schulz, Committee Chair, Dr. Joseph OTousa, Committee Member, Dr. David Hyde, Committee Member.

Subjects/Keywords: Drosophila; genetics; bag-of-margles; hematopoiesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hopkins, D. W. (2014). The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/ng451g07s8m

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hopkins, Dawn Weseli. “The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>.” 2014. Thesis, University of Notre Dame. Accessed March 04, 2021. https://curate.nd.edu/show/ng451g07s8m.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hopkins, Dawn Weseli. “The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>.” 2014. Web. 04 Mar 2021.

Vancouver:

Hopkins DW. The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>. [Internet] [Thesis]. University of Notre Dame; 2014. [cited 2021 Mar 04]. Available from: https://curate.nd.edu/show/ng451g07s8m.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hopkins DW. The Genetic Control of Hematopoietic Progenitor Fate in <i>Drosophila</i></h1>. [Thesis]. University of Notre Dame; 2014. Available from: https://curate.nd.edu/show/ng451g07s8m

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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