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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Huang X. Distinct Roles of Cellular Copper and Erythropoietin Receptor on Hematopoietic Engraftment. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2019 Dec 11]. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Lim Y. Translating insights from normal, neoplastic hematopoiesis and myeloid disease progression into potential clinical applications. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2019 Dec 11]. 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 Hong Kong

3. 文岐方; Man, Ki-fong. The role of calreticulin (CALR) in vertebrate hematopoiesis.

Degree: M. Phil., 2016, University of Hong Kong

URL: Man, K. [文岐方]. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816263. ; http://dx.doi.org/10.5353/th_b5816263 ; 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 (6^th Edition):

文岐方; Man, K. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Masters Thesis). University of Hong Kong. Retrieved from Man, K. [文岐方]. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816263. ; http://dx.doi.org/10.5353/th_b5816263 ; http://hdl.handle.net/10722/237867

Chicago Manual of Style (16^th Edition):

文岐方; Man, Ki-fong. “The role of calreticulin (CALR) in vertebrate hematopoiesis.” 2016. Masters Thesis, University of Hong Kong. Accessed December 11, 2019. Man, K. [文岐方]. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816263. ; http://dx.doi.org/10.5353/th_b5816263 ; http://hdl.handle.net/10722/237867.

MLA Handbook (7^th Edition):

文岐方; Man, Ki-fong. “The role of calreticulin (CALR) in vertebrate hematopoiesis.” 2016. Web. 11 Dec 2019.

Vancouver:

文岐方; Man K. The role of calreticulin (CALR) in vertebrate hematopoiesis. [Internet] [Masters thesis]. University of Hong Kong; 2016. [cited 2019 Dec 11]. Available from: Man, K. [文岐方]. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816263. ; http://dx.doi.org/10.5353/th_b5816263 ; http://hdl.handle.net/10722/237867.

Council of Science Editors:

文岐方; Man K. The role of calreticulin (CALR) in vertebrate hematopoiesis. [Masters Thesis]. University of Hong Kong; 2016. Available from: Man, K. [文岐方]. (2016). The role of calreticulin (CALR) in vertebrate hematopoiesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816263. ; http://dx.doi.org/10.5353/th_b5816263 ; http://hdl.handle.net/10722/237867

University of Hong Kong

4. Zhang, Jingxuan. Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis.

Degree: PhD, 2014, University of Hong Kong

URL: Zhang, J. [張璟璇]. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5328059 ; http://dx.doi.org/10.5353/th_b5328059 ; http://hdl.handle.net/10722/206751

► Post-translational modifications of histone proteins serve as one of the key epigenetic regulatory mechanisms in the development of organisms. It is well-known that methylation on… (more)

▼ Post-translational modifications of histone proteins serve as one of the key epigenetic regulatory mechanisms in the development of organisms. It is well-known that methylation on histone lysine residues is an important epigenetic modification for the transcriptional regulation of normal hematopoiesis and leukemogenesis. JARID1B, a member of the JARID1 histone H3 lysine 4 (H3K4) demethylases, was found essential for the self-renewal of both embryonic stem cell and melanoma stem-like cell, and was involved in regulating genes, such as Egr1, Bmi-1 and p27, during embryo development. In addition, JARID1B is involved in the differentiation of neural cells and macrophages. Although JARID1B is believed to have important functions in stem cell biology, its role in hematopoiesis and leukemogenesis has not been systematically studied. We therefore examined the expression profile of JARID1B in different hematopoietic lineage cells. We observed an up-regulation of JARID1B in differentiated hematopoietic cells by comparing with hematopoietic stem cells and progenitor cells, suggesting that the enhanced cellular level of JARID1B is associated with hematopoietic lineage commitment. Interestingly, JARID1B expression is generally low in human leukemia cell lines and in CML (Chronic Myeloid leukemia) patient samples compared to 〖CD34〗^+ cord blood cells and normal peripheral white blood cells, which indicates the down-regulation of JARID1B is associated with leukemia development. We further modulated the expression of JARID1B in human leukemia cell lines, K562 and SEM, and in mouse hematopoietic stem/progenitor cells (〖Lin〗^-/〖Sca〗^(-1+)/c-〖Kit〗^+, LSK cells). We found that knockdown of Jarid1b in LSK cells did not alter their cell-cycle pattern. However, total colony formation number was reduced in serial re-plating assays, suggesting Jarid1b is required for the maintenance of colony-forming ability and self-renewal property. Knockdown of JARID1B in K562 cells did not change their cell proliferation and cell-cycle pattern, but did consistently inhibit their colony-forming ability during serial re-plating assays. On the other hand, overexpression of JARID1B in K562 and SEM leukemic cells inhibited cell proliferation and colony formation, but with no significant changes on cell-cycle patterns. Furthermore, apoptosis staining did not show any correlations between JARID1B overexpression and apoptosis. Previously, JARID1A, another JARID1 family member, was found as a fusion partner in AML (Acute Myeloid Leukemia); its third PHD domain, which locates at C-terminus, is associated with leukemogenesis. By amino acid sequence alignment, the differences between JARID1A and JARID1B protein are mainly occurred at their C-terminal regions, after the second PHD domain. Therefore, GST fusion protein pull-down experiments for this region was performed. Preliminary results showed that the C-terminus of JARID1B protein interacts with proteins of RNA transcriptional machinery complex. However, further investigation is needed to demonstrate these… Advisors/Committee Members: Chan, LC, Ng, RK.

Subjects/Keywords: Hematopoiesis; Histones; Leukemia

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APA (6^th Edition):

Zhang, J. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Doctoral Dissertation). University of Hong Kong. Retrieved from Zhang, J. [張璟璇]. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5328059 ; http://dx.doi.org/10.5353/th_b5328059 ; http://hdl.handle.net/10722/206751

Chicago Manual of Style (16^th Edition):

Zhang, Jingxuan. “Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis.” 2014. Doctoral Dissertation, University of Hong Kong. Accessed December 11, 2019. Zhang, J. [張璟璇]. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5328059 ; http://dx.doi.org/10.5353/th_b5328059 ; http://hdl.handle.net/10722/206751.

MLA Handbook (7^th Edition):

Zhang, Jingxuan. “Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis.” 2014. Web. 11 Dec 2019.

Vancouver:

Zhang J. Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. [Internet] [Doctoral dissertation]. University of Hong Kong; 2014. [cited 2019 Dec 11]. Available from: Zhang, J. [張璟璇]. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5328059 ; http://dx.doi.org/10.5353/th_b5328059 ; http://hdl.handle.net/10722/206751.

Council of Science Editors:

Zhang J. Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. [Doctoral Dissertation]. University of Hong Kong; 2014. Available from: Zhang, J. [張璟璇]. (2014). Studies of histone demethylase JARID1B in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5328059 ; http://dx.doi.org/10.5353/th_b5328059 ; http://hdl.handle.net/10722/206751

Universiteit Utrecht

5. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Lange TAD. The role of Cdx in embryonic and adult mammalian hematopoiesis. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2019 Dec 11]. 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 Hong Kong

6. 陳國熙; Chan, Kwok-hei. Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome.

Degree: Master of Research in Medicine, Medicine, 2017, University of Hong Kong

URL: http://hdl.handle.net/10722/251321

►

Autophagy is a conserved cellular mechanism essential for degrading expired cytoplasmic constituents and plays a pivotal role in haematopoiesis and haemic malignancies. It is putatively… (more)

▼

Autophagy is a conserved cellular mechanism essential for degrading expired cytoplasmic constituents and plays a pivotal role in haematopoiesis and haemic malignancies. It is putatively implicated in the pathogenesis of myelodysplastic syndrome because cellular sequelae of deranged autophagy were observed in the patients’ bone marrow cells. It was found that Atg7 and FIP200, which mediate two different stages of autophagy, were required for haematopoietic stem cell maintenance and differentiation; conditional knockout of these two proteins induced anaemia and atypical myeloproliferation in murine models. However, in the zebrafish model, functional studies of autophagy-related genes are lacking and the precise role of autophagy in haematopoiesis is yet to be clarified. This study examined the zebrafish homologues, atg7 and atg13, in the context of embryonic haematopoiesis. Spatial and temporal expression of atg7 and atg13 was determined by whole-mount in situ hybridisation and polymerase chain reaction. Knockdown of atg7 and atg13 was conducted by translation-blocking morpholino oligomers. Molecular targeting of the morpholino oligomers was validated by quenching the co-injected fusion fluorescent reporter plasmids. In phenotypic examination, no aberration of primitive and definitive haematopoiesis was induced by atg7-knockdown and atg13-knockdown. Moreover, two biochemical assays of autophagy, LysoTracker and Autophagy Detection Kit, were evaluated on drug-treated and morphant embryos. LysoTracker staining of autophagy-suppressed embryos displayed significantly reduced fluorescent signals and demonstrated autophagy suppression in morphant embryos. However, Autophagy Detection Kit produced non-specific signals and thus was not recommended for assaying autophagy. Similarly, double-staining of wildtype embryos failed to produce satisfactory co-localisation signals under confocal microscopy. This study suggests that transient autophagy suppression by morpholino knockdown does not readily affect embryonic haematopoiesis and LysoTracker is a satisfactory autophagy assay. To overcome the limitations encountered in this study, it warrants knockout models for evaluating the long-term effects of autophagy ablation and transgenic fluorescent reporter lines for monitoring autophagy activity in concert with LysoTracker.

published_or_final_version

Medicine

Master

Master of Research in Medicine

Subjects/Keywords: Autophagic vacuoles; Myelodysplastic syndromes; Hematopoiesis

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APA (6^th Edition):

陳國熙; Chan, K. (2017). Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome. (Masters Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/251321

Chicago Manual of Style (16^th Edition):

陳國熙; Chan, Kwok-hei. “Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome.” 2017. Masters Thesis, University of Hong Kong. Accessed December 11, 2019. http://hdl.handle.net/10722/251321.

MLA Handbook (7^th Edition):

陳國熙; Chan, Kwok-hei. “Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome.” 2017. Web. 11 Dec 2019.

Vancouver:

陳國熙; Chan K. Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome. [Internet] [Masters thesis]. University of Hong Kong; 2017. [cited 2019 Dec 11]. Available from: http://hdl.handle.net/10722/251321.

Council of Science Editors:

陳國熙; Chan K. Role of autophagy in vertebrate haematopoiesis and human myelodysplastic syndrome. [Masters Thesis]. University of Hong Kong; 2017. Available from: http://hdl.handle.net/10722/251321

University of Hong Kong

7. Wan, Haixia. Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia.

Degree: PhD, 2012, University of Hong Kong

URL: Wan, H. [万海霞]. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137970 ; http://dx.doi.org/10.5353/th_b5137970 ; http://hdl.handle.net/10722/194606

►

The SOX (Sry-related HMG box) genes belong to a family of transcription factors containing a High-Mobility-Group box domain. In an initial screen, SOX7 was uniquely… (more)

▼

The SOX (Sry-related HMG box) genes belong to a family of transcription factors containing a High-Mobility-Group box domain. In an initial screen, SOX7 was uniquely down-regulated in myeloid malignancies compared with most cases of precursor B-cell acute lymphoblastic leukemia (ALL) and normal bone marrow cell, leading us to examine the expression and function of SOX7 during normal hematopoietic differentiation and in acute lymphoblastic leukemia. By studying human umbilical cord blood (UCB), SOX7 expression in different hematopoietic lineages was evaluated by RT-PCR. SOX7 was preferentially expressed in CD34+CD38- compared with CD34+CD38+ population and in CD34-CD19+ compared with CD34-CD33+ cells. SOX7 expression was down-regulated in colonies in CFU assay and in engrafting myeloid cells in NOD/SCID mouse transplantation. Transfecting SOX7 siRNA into CD34+ cells reduced cell growth and the CD34+CD33+ population in 3-day culture; induced cell-cycle arrest at G1 phase; reduced clonogenic activities but had no effect on apoptosis. Overall engraftment into NOD/SCID mice were not affected but the engrafting myeloid populations were reduced. In acute lymphoblastic leukemia, SOX7 was robustly expressed, compared with that in normal UCB and acute myeloid leukemia (AML). In 5 ALL patients in whom the coding sequence of SOX7 was examined, 3 of them showed mutations (amino acid change) in the SOX C-terminal transactivation domain. No mutation was observed in the β-catenin binding site. Knockdown of SOX7 with specific siRNA significantly increased appoptosis and decreased cell proliferation. SOX7 knockdown by shRNA in a precursor B-cell ALL cell line Nalm20 significantly reduced its engraftment into NOD/SCID mice. In summary, SOX7 is preferentially expressed in early hematopoietic stem and progenitor cells and is important for the maintenance of myeloid progenitor. It is also expressed in the primitive population of ALL and is important for leukemia initiation in ALL. The present study has generated important information about the regulation of normal hematopoiesis and acute lymphoblastic leukemia

published_or_final_version

Medicine

Doctoral

Doctor of Philosophy

Advisors/Committee Members: Leung, AYH.

Subjects/Keywords: Hematopoiesis; Lymphoblastic leukemia - Genetic aspects

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

APA (6^th Edition):

Wan, H. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Doctoral Dissertation). University of Hong Kong. Retrieved from Wan, H. [万海霞]. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137970 ; http://dx.doi.org/10.5353/th_b5137970 ; http://hdl.handle.net/10722/194606

Chicago Manual of Style (16^th Edition):

Wan, Haixia. “Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia.” 2012. Doctoral Dissertation, University of Hong Kong. Accessed December 11, 2019. Wan, H. [万海霞]. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137970 ; http://dx.doi.org/10.5353/th_b5137970 ; http://hdl.handle.net/10722/194606.

MLA Handbook (7^th Edition):

Wan, Haixia. “Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia.” 2012. Web. 11 Dec 2019.

Vancouver:

Wan H. Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. [Internet] [Doctoral dissertation]. University of Hong Kong; 2012. [cited 2019 Dec 11]. Available from: Wan, H. [万海霞]. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137970 ; http://dx.doi.org/10.5353/th_b5137970 ; http://hdl.handle.net/10722/194606.

Council of Science Editors:

Wan H. Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. [Doctoral Dissertation]. University of Hong Kong; 2012. Available from: Wan, H. [万海霞]. (2012). Function of SOX7 in normal hematopoiesis and in acute lymphoblastic leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137970 ; http://dx.doi.org/10.5353/th_b5137970 ; http://hdl.handle.net/10722/194606

University of Hong Kong

8. Lam, Yuk-man. Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis.

Degree: PhD, 2014, University of Hong Kong

URL: Lam, Y. [林旭文]. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387952 ; http://dx.doi.org/10.5353/th_b5387952 ; http://hdl.handle.net/10722/222770

► Bmi-1 maintains stem cell population in hematopoietic system for replenishment of progenitors and mature cells. It has been shown that Bmi-1 prevents stem cell exhaustion… (more)

▼ Bmi-1 maintains stem cell population in hematopoietic system for replenishment of progenitors and mature cells. It has been shown that Bmi-1 prevents stem cell exhaustion through suppression of cell cycle regulators 〖p16〗^INK4a/ 〖p19〗^Arf and cell differentiation. However, it remains unclear how Bmi-1 maintains self-renewal of hematopoietic stem cells (HSC). To dissect the underlying mechanisms of Bmi-1 in sustaining HSC self-renewal capacity, transcriptome analysis of Bmi-1 knockdown or over-expressing hematopoietic stem and progenitor cells (HSPC) was performed. RNA-Sequencing analysis demonstrated that Bmi-1 de-regulated genes in canonical Wnt signaling, stem-cell quiescence and Tnf/Gzmb-mediated apoptotic signaling in HSPC. Moreover, it was found that Bmi-1 over-expression mildly activated canonical Wnt signaling and de-regulated a panel of Wnt-associated genes Cdkn1a, n-Myc, Fn-1 and Hoxb4 in HSPC. ChIP analysis validated that Bmi-1 binds to the promoter region of Wnt negative regulator Amer2. It suggests that Bmi-1 activates canonical Wnt signaling through suppression of Amer2 in HSPC. More importantly, ChIP analysis validated that Bmi-1 binds to its own promoter region, suggesting that endogenous Bmi-1 expression is maintained through self-regulatory negative feedback mechanism to prevent excessive Wnt signaling activation in HSPC. In view of this, a model of Bmi-1-mediated suppression of Amer2-dependent β-catenin degradation in HSC is proposed. On the other hand, BMI-1-mediated 〖p16〗^INK4A leukemogenic pathway has been proposed in human leukemias. However, clinical studies revealed that high BMI-1 expression may not be well-correlated with low 〖p16〗^INK4A expression. Importantly, leukemogenic factors such as MLL fusion proteins can regulate 〖p16〗^INK4A expression such that the regulation of 〖p16〗^INK4A is not dependent on BMI-1. It is therefore unclear how BMI-1 is involved in the process of leukemogenesis. Although it has been demonstrated that high BMI-1 expression was correlated with disease development in human leukemias, recent studies revealed a tumor suppressive role of BMI-1 in cancers, questioning the role of BMI-1 in leukemogenesis. In order to find out the regulatory mechanism of BMI-1 in leukemogenesis, BMI-1 was overexpressed in a panel of leukemia cell lines, including HL-60, MonoMac-6, MV4-11, SEM and Nalm-6. My results demonstrated that BMI-1 over-expression suppresses JAK-STAT signaling through up-regulation of SOCS genes. Moreover, it was found that BMI-1 over-expression suppresses IL7 signaling pathway in SEM leukemia cells, leading to reduced expression of cell survival genes, including PAX5, MCL-1, BCL-2 and BCL-XL. These findings suggest that BMI-1 has a tumor suppressive function in leukemogenesis. In summary, the discoveries of Bmi-1-mediated canonical Wnt signaling and the suppressive role of BMI-1 in JAK-STAT leukemogenic signaling would provide new insights on the understanding of stem cell and leukemia biology, building a foundation for improvement of clinical…

Subjects/Keywords: Leukemia; Hematopoiesis; Chromosomal proteins

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

APA (6^th Edition):

Lam, Y. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Doctoral Dissertation). University of Hong Kong. Retrieved from Lam, Y. [林旭文]. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387952 ; http://dx.doi.org/10.5353/th_b5387952 ; http://hdl.handle.net/10722/222770

Chicago Manual of Style (16^th Edition):

Lam, Yuk-man. “Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis.” 2014. Doctoral Dissertation, University of Hong Kong. Accessed December 11, 2019. Lam, Y. [林旭文]. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387952 ; http://dx.doi.org/10.5353/th_b5387952 ; http://hdl.handle.net/10722/222770.

MLA Handbook (7^th Edition):

Lam, Yuk-man. “Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis.” 2014. Web. 11 Dec 2019.

Vancouver:

Lam Y. Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. [Internet] [Doctoral dissertation]. University of Hong Kong; 2014. [cited 2019 Dec 11]. Available from: Lam, Y. [林旭文]. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387952 ; http://dx.doi.org/10.5353/th_b5387952 ; http://hdl.handle.net/10722/222770.

Council of Science Editors:

Lam Y. Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. [Doctoral Dissertation]. University of Hong Kong; 2014. Available from: Lam, Y. [林旭文]. (2014). Distinctive functions of the polycomb group protein BMI-1 in hematopoiesis and leukemogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387952 ; http://dx.doi.org/10.5353/th_b5387952 ; http://hdl.handle.net/10722/222770

University of Southern California

9. 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/7209

► 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/7209

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 December 11, 2019. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7209.

MLA Handbook (7^th Edition):

Wey, Shiuan. “The role of endoplasmic reticulum protein GRP78 in normal hematopoeises and PTEN-null leukemogenesis.” 2013. Web. 11 Dec 2019.

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 2019 Dec 11]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/629905/rec/7209.

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/7209

McMaster University

10. Baker, Jeff. The effects of exercise on hematopoiesis.

Degree: PhD, 2017, McMaster University

URL: http://hdl.handle.net/11375/21999

►

Exercise has been shown to influence nearly every tissue type in the body, including the hematopoietic system. The means by and the extent to which… (more)

▼

Exercise has been shown to influence nearly every tissue type in the body, including the hematopoietic system. The means by and the extent to which exercise is able to do this is unknown. Here, we investigated the effects of skeletal muscle and exercise on several components of hematopoiesis. Firstly, we investigated exercise induced changes in skeletal muscle endocrine signalling. We demonstrated that exercise increased skeletal muscle hypoxia, leading to HIF1α and HIF2α stability, resulting in increased expression of erythropoietin. As well, myoblasts in culture were shown to express and release erythropoietin in response to hypoxia. Secondly, we measured mobilization of hematopoietic cells during exercise. We demonstrated that exercise greatly increased the number of hematopoietic stem cells in circulation. The quantity of mobilization was dependent on exercise intensity, did not depend on fitness levels, and was at peak immediately post exercise. Thirdly, we measured levels of extramedullary hematopoiesis following exercise. Exercise increased spleen hematopoietic stem cell content. Furthermore, expression of genes associated with hematopoietic homing, adhesion, quiescence, and growth were all increased in the spleen following exercise. Finally, we examined bone marrow in the appendicular and axial skeleton of aged animals. Here, exercise increased bone marrow cellularity and reduced bone marrow adiposity in the appendicular skeleton of aged mice. However, lumbar vertebral marrow cellularity and skeletal muscle expression of hematopoietic cytokines in these mice was unaffected by exercise. Taken together, these results demonstrate that exercise is a potent mediator of hematopoietic homeostasis. Several themes recurrent in these and other studies lead to insight in how exercise is able to exert influence on hematopoiesis, namely: tissue specific changes in hematopoietic growth and homing factor expression, the ability of mechanical forces felt during exercise to alter the bone marrow niche microenvironment, and increased flux of hematopoietic stem cells through their various bodily niches.

Thesis

Doctor of Philosophy (PhD)

Exercise affects many different tissue types throughout the body. The hematopoietic system, through which the body produces blood cells, is no exception. How exercise as a stimulus is able to influence this system is poorly understood. Here, we demonstrate that exercise is able to stimulate skeletal muscle to produce erythropoietin, a potent hematopoietic growth factor. As well, we demonstrate that exercise is capable of mobilizing hematopoietic stem cells from the bone marrow to the blood. We then describe how exercise is able to increase hematopoietic activity outside the bone marrow. Finally, we show that exercise affects marrow in only certain bone marrow cavities. Our findings demonstrate that exercise is able to influence hematopoiesis in a myriad of ways. As well, our findings highlight potential commonalities in the means by which exercise exerts these influences.

Advisors/Committee Members: Parise, Gianni, Kinesiology.

Subjects/Keywords: hematopoiesis; exercise; bone; muscle

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

APA (6^th Edition):

Baker, J. (2017). The effects of exercise on hematopoiesis. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/21999

Chicago Manual of Style (16^th Edition):

Baker, Jeff. “The effects of exercise on hematopoiesis.” 2017. Doctoral Dissertation, McMaster University. Accessed December 11, 2019. http://hdl.handle.net/11375/21999.

MLA Handbook (7^th Edition):

Baker, Jeff. “The effects of exercise on hematopoiesis.” 2017. Web. 11 Dec 2019.

Vancouver:

Baker J. The effects of exercise on hematopoiesis. [Internet] [Doctoral dissertation]. McMaster University; 2017. [cited 2019 Dec 11]. Available from: http://hdl.handle.net/11375/21999.

Council of Science Editors:

Baker J. The effects of exercise on hematopoiesis. [Doctoral Dissertation]. McMaster University; 2017. Available from: http://hdl.handle.net/11375/21999

University of Washington

11. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Duggan JM. BCAP functions as a dynamic regulator of hematopoiesis and myeloid cell development. [Internet] [Doctoral dissertation]. University of Washington; 2017. [cited 2019 Dec 11]. 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

McMaster University

12. 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

►

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)

▼

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 December 11, 2019. 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. 11 Dec 2019.

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 2019 Dec 11]. 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 British Columbia

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

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

APA (6^th Edition):

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

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):

Hogge, Donna Eileen. “Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors .” 1987. Thesis, University of British Columbia. Accessed December 11, 2019. http://hdl.handle.net/2429/27316.

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

MLA Handbook (7^th Edition):

Hogge, Donna Eileen. “Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors .” 1987. Web. 11 Dec 2019.

Vancouver:

Hogge DE. Genetic investigations of human hemopoiesis : studies of clonality and gene transfer to hemopoietic progenitors . [Internet] [Thesis]. University of British Columbia; 1987. [cited 2019 Dec 11]. Available from: http://hdl.handle.net/2429/27316.

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

Council of Science Editors:

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

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

Loyola University Chicago

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

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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Birch NW. Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity. [Internet] [Doctoral dissertation]. Loyola University Chicago; 2013. [cited 2019 Dec 11]. 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

University of Ottawa

15. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Rothberg JL. Polycomb-like 2 (Mtf2/Pcl2) is Required for Epigenetic Regulation of Hematopoiesis . [Internet] [Thesis]. University of Ottawa; 2016. [cited 2019 Dec 11]. 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 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Ang CH. Role of Npm1 in normal hematopoiesis and acute myeloid leukemia. [Internet] [Doctoral dissertation]. University of Melbourne; 2016. [cited 2019 Dec 11]. 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

17. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

YIN-KUAN AH. DIRECTED REPROGRAMMING OF FIBROBLASTS INTO HEMATOPOIETIC PROGENITORS BY NUCLEAR REGULATORS. [Internet] [Thesis]. National University of Singapore; 2012. [cited 2019 Dec 11]. 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

University of Toronto

18. 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

►

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 December 11, 2019. 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. 11 Dec 2019.

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 2019 Dec 11]. 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 Rochester

19. 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 December 11, 2019. http://hdl.handle.net/1802/21468.

MLA Handbook (7^th Edition):

Peslak, Scott Alan. “Erythropoiesis: Injury and Recovery.” 2012. Web. 11 Dec 2019.

Vancouver:

Peslak SA. Erythropoiesis: Injury and Recovery. [Internet] [Doctoral dissertation]. University of Rochester; 2012. [cited 2019 Dec 11]. 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

University of Notre Dame

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

Degree: MS, 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>. (Masters Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/k6439z92b62

Chicago Manual of Style (16^th Edition):

Stoller-Conrad, Jessica Renee. “Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>.” 2012. Masters Thesis, University of Notre Dame. Accessed December 11, 2019. https://curate.nd.edu/show/k6439z92b62.

MLA Handbook (7^th Edition):

Stoller-Conrad, Jessica Renee. “Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>.” 2012. Web. 11 Dec 2019.

Vancouver:

Stoller-Conrad JR. Determination and Characterization of Novel Genes Influencing Drosophila Hematopoietic Development</h1>. [Internet] [Masters thesis]. University of Notre Dame; 2012. [cited 2019 Dec 11]. Available from: https://curate.nd.edu/show/k6439z92b62.

Council of Science Editors:

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

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

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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

JIN X. Study of definitive hematopoiesis in zebrafish. [Internet] [Thesis]. National University of Singapore; 2008. [cited 2019 Dec 11]. 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 Rochester

22. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Frame JM. Emergence and Regulation of Hemogenic Endothelium in the Mammalian Yolk Sac. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2019 Dec 11]. 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

23. 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 (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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Buchrieser J. Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs). [Internet] [Doctoral dissertation]. University of Oxford; 2016. [cited 2019 Dec 11]. 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

24. 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 December 11, 2019. 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. 11 Dec 2019.

Vancouver:

Pillay LM. Functional Characterization of Homeodomain Transcription Factors and Retinoic Acid Signaling in Hematopoiesis. [Internet] [Doctoral dissertation]. University of Alberta; 2015. [cited 2019 Dec 11]. 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

University of Kansas

25. Miller, Kyle Lamar. SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR.

Degree: MS, Preventive Medicine and Public Health, 2013, University of Kansas

URL: http://hdl.handle.net/1808/12271

► A novel mutant mouse called X-linked pre- and neonatal anemia (gene symbol, Xpna) results in a transient, neonatal anemia which is resolved by 3 weeks… (more)

Subjects/Keywords: Genetics; Erythropoiesis; Gata-1; Hematopoiesis; Transcription factors

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APA (6^th Edition):

Miller, K. L. (2013). SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/12271

Chicago Manual of Style (16^th Edition):

Miller, Kyle Lamar. “SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR.” 2013. Masters Thesis, University of Kansas. Accessed December 11, 2019. http://hdl.handle.net/1808/12271.

MLA Handbook (7^th Edition):

Miller, Kyle Lamar. “SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR.” 2013. Web. 11 Dec 2019.

Vancouver:

Miller KL. SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR. [Internet] [Masters thesis]. University of Kansas; 2013. [cited 2019 Dec 11]. Available from: http://hdl.handle.net/1808/12271.

Council of Science Editors:

Miller KL. SPLICING ERROR IN GATA1 AFFECTS ERYTHROPOIESIS IN THE XPNA MOUSE (X-LINKED PRE- AND NEONATAL ANEMIA) WITH SUGGESTION OF A NOVEL COMPENSATORY ERYTHROID TRANSCRIPTION FACTOR. [Masters Thesis]. University of Kansas; 2013. Available from: http://hdl.handle.net/1808/12271

University of Western Australia

26. Cheung, Chun Ting Laurence. The role of connective tissue growth factor in hematopoiesis.

Degree: PhD, 2014, University of Western Australia

URL: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=40194&local_base=GEN01-INS01

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[Truncated abstract] Background: Hematopoiesis is a tightly regulated multi-stage process, predominantly occurring in fetal liver before birth and in the bone marrow postnatally. All hematopoietic… (more)

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[Truncated abstract] Background: Hematopoiesis is a tightly regulated multi-stage process, predominantly occurring in fetal liver before birth and in the bone marrow postnatally. All hematopoietic cells are derived from a small population of hematopoietic stem cells (HSCs), in which the differentiation and self-renewal properties of HSCs are governed by signals derived from cellular and acellular components that constitute the complex bone marrow microenvironment or niches. Bone marrow stromal cells (BMSCs), osteoblastic cells and endothelial cells critically support the process via direct cell contact, cytokines and growth factors. Connective tissue growth factor (CTGF) is an extracellular matrix-associated protein that is known to regulate skeletogenesis, angiogenesis, osteoclastogenesis as well as osteoblastogenesis in the bone marrow microenvironment, and has been implicated in hematopoietic malignancy, however its role in hematopoiesis has not been determined. Methods: Hematopoietic system in Ctgf+/- and Ctgf-/- mice was examined. Using multi-colour flow cytometric analyses, different lineage populations in various hematopoietic organs from Ctgf-/- and wild type (WT) mice were enumerated. Because Ctgf-/- mice died perinatally, the hematopoietic potential of cells from Ctgf-/- and WT fetal livers was compared using chimera transplantation models. Furthermore, mRNA expression of Ctgf was examined in the bone marrow compartment. In order to gain insight into the function of Ctgf in the bone marrow microenvironment, B-cell maturation was examined in a novel Ctgf-/- BMSC culture system. Lastly, the regulatory role of CTGF in B-cell development was investigated in vitro using recombinant CTGF and IL-7...

[Truncated abstract] Background: Hematopoiesis is a tightly regulated multi-stage process, predominantly occurring in fetal liver before birth and in the bone marrow postnatally. All hematopoietic cells are derived from a small population of hematopoietic stem cells (HSCs), in which the differentiation and self-renewal properties of HSCs are governed by signals derived from cellular and acellular components that constitute the complex bone marrow microenvironment or niches. Bone marrow stromal cells (BMSCs), osteoblastic cells and endothelial cells critically support the process via direct cell contact, cytokines and growth factors. Connective tissue growth factor (CTGF) is an extracellular matrix-associated protein that is known to regulate skeletogenesis, angiogenesis, osteoclastogenesis as well as osteoblastogenesis in the bone marrow microenvironment, and has been implicated in hematopoietic malignancy, however its role in hematopoiesis has not been determined. Methods: Hematopoietic system in Ctgf+/- and Ctgf-/- mice was examined. Using multi-colour flow cytometric analyses, different lineage populations in various hematopoietic organs from Ctgf-/- and wild type (WT) mice were enumerated. Because Ctgf-/- mice died perinatally, the hematopoietic potential of cells from Ctgf-/- and WT fetal livers was…

Subjects/Keywords: Connective tissue growth factor; Hematopoiesis; B lymphopoiesis

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

APA (6^th Edition):

Cheung, C. T. L. (2014). The role of connective tissue growth factor in hematopoiesis. (Doctoral Dissertation). University of Western Australia. Retrieved from http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=40194&local_base=GEN01-INS01

Chicago Manual of Style (16^th Edition):

Cheung, Chun Ting Laurence. “The role of connective tissue growth factor in hematopoiesis.” 2014. Doctoral Dissertation, University of Western Australia. Accessed December 11, 2019. http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=40194&local_base=GEN01-INS01.

MLA Handbook (7^th Edition):

Cheung, Chun Ting Laurence. “The role of connective tissue growth factor in hematopoiesis.” 2014. Web. 11 Dec 2019.

Vancouver:

Cheung CTL. The role of connective tissue growth factor in hematopoiesis. [Internet] [Doctoral dissertation]. University of Western Australia; 2014. [cited 2019 Dec 11]. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=40194&local_base=GEN01-INS01.

Council of Science Editors:

Cheung CTL. The role of connective tissue growth factor in hematopoiesis. [Doctoral Dissertation]. University of Western Australia; 2014. Available from: http://repository.uwa.edu.au:80/R/?func=dbin-jump-full&object_id=40194&local_base=GEN01-INS01

University of Hong Kong

27. 何柏亮; He, Bailiang. Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML.

Degree: PhD, 2015, University of Hong Kong

URL: He, B. [何柏亮]. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5719465 ; http://hdl.handle.net/10722/223584

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FMS-like tyrosine kinase 3 (FLT3) is expressed in human hematopoietic stem and progenitor cells (HSPC) but its role during embryogenesis is unclear. In acute myeloid… (more)

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FMS-like tyrosine kinase 3 (FLT3) is expressed in human hematopoietic stem and progenitor cells (HSPC) but its role during embryogenesis is unclear. In acute myeloid leukemia (AML), internal tandem duplications (ITD) of FLT3 at the juxtamembrane domain (JMD) (FLT3/ITD) occur in 30% of patients and are associated with inferior clinical prognosis. Tyrosine kinase domain (TKD) mutations (FLT3/TKD) occur in 5% of cases and their prognostic significance is unclear. Both mutations result in constitutive activation of FLT3 signaling. In this project, zebrafish was used to examine the role of flt3 in developmental hematopoiesis and model human FLT3/ITD+ and FLT3/TKD+ AML in this organism. The JMD and TKD regions of zebrafish Flt3 were remarkably similar to their mammalian counterparts. Knockdown of flt3 by morpholino significantly reduced the expression of l-plastin (pan-leukocyte), csf1r and mpeg1 (macrophage) as well as that of c-myb (definitive HSPC), lck and rag1 (T-lymphocyte) shown by whole mount in situ hybridization (WISH). Expression of human FLT3/ITD in zebrafish embryos by plasmid DNA injection resulted in Stat5, Erk1/2, and Akt phosphorylation and the expansion of myeloid cells (pu.1+, mpo+, and cebpα+). The latter was ameliorated by FLT3 inhibitor quizartinib (formerly AC220). Human FLT3/TKD (D835Y) induced significant, albeit modest, myeloid expansion resistant to quizartinib, corroborating with their clinical responses to FLT3 inhibitors. Intriguingly, injection of FLT3/ITD mRNA induced dorsal axis duplication with duplicated expression of notochord marker col9a2 at 24 hours-post-fertilization (hpf). The effects could be ameliorated by quizartinib. To identify the initiating signals associated with axis duplication, expression of genes associated with dorsoventral patterning was examined at shield stage (6 hpf). The Spemann’s organizer was expanded as evidenced by increased and ectopic expression of goosecoid (gsc), chordin (chd) and follistatin (fst). The up-regulation of Fst was confirmed by quantitative RT-QPCR and Western Blot. Interestingly, FST protein expression and STAT5 phosphorylation were significantly up-regulated in FLT3/ITD-transfected Hela cells, as well as in BaF3 cells expressing FLT3/ITD and FLT3/ITD+ AML cell lines MV4-11 and MOLM-13. FST transcript, protein expression (in cell) and protein secretion (in serum) were significantly increased in FLT3/ITD+ AML samples. Importantly, quizartinib significantly inhibited FST expression and FST knockdown significantly reduced leukemia growth of MV4-11 cells in vitro. This study provided novel insight to the role of flt3 during hematopoiesis, established a zebrafish model expressing of FLT3/ITD and FLT3/TKD mutation from AML, and identified FST as a novel molecular target of FLT3/ITD+ AML whose therapeutic potential should be further evaluated.

published_or_final_version

Medicine

Doctoral

Doctor of Philosophy

Subjects/Keywords: Zebra danio - Embryos; Protein-tyrosine kinase; Hematopoiesis

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

APA (6^th Edition):

何柏亮; He, B. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Doctoral Dissertation). University of Hong Kong. Retrieved from He, B. [何柏亮]. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5719465 ; http://hdl.handle.net/10722/223584

Chicago Manual of Style (16^th Edition):

何柏亮; He, Bailiang. “Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML.” 2015. Doctoral Dissertation, University of Hong Kong. Accessed December 11, 2019. He, B. [何柏亮]. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5719465 ; http://hdl.handle.net/10722/223584.

MLA Handbook (7^th Edition):

何柏亮; He, Bailiang. “Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML.” 2015. Web. 11 Dec 2019.

Vancouver:

何柏亮; He B. Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. [Internet] [Doctoral dissertation]. University of Hong Kong; 2015. [cited 2019 Dec 11]. Available from: He, B. [何柏亮]. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5719465 ; http://hdl.handle.net/10722/223584.

Council of Science Editors:

何柏亮; He B. Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. [Doctoral Dissertation]. University of Hong Kong; 2015. Available from: He, B. [何柏亮]. (2015). Functional study of zebrafish Flt3 in embryonic hematopoiesis with particular reference to modeling human FLT3/ITD AML. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5719465 ; http://hdl.handle.net/10722/223584

University of Hong Kong

28. Man, Hon-wai. A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4).

Degree: Master of Medical Sciences, 2011, University of Hong Kong

URL: Man, H. [文漢威]. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4777052 ; http://dx.doi.org/10.5353/th_b4777052 ; http://hdl.handle.net/10722/174500

► Zebrafish has emerged as an important vertebrate model for studying hematopoiesis and its genetic and chemical modifiers. The zebrafish embryos are unique in their optical… (more)

▼ Zebrafish has emerged as an important vertebrate model for studying hematopoiesis and its genetic and chemical modifiers. The zebrafish embryos are unique in their optical transparency, ease of maintenance and high fecundity. They are also amendable to genetic and pharmacological perturbation at high throughput. As a result, the embryos are suitable for various experimental techniques and have a high efficiency in large-scale drug screening. Recently, zebrafish has also emerged as a model for the study of human disease. In this model organism, primitive hematopoiesis is transitory and it occurs in the intermediate cells mass and comprises primarily erythroid cells. Definitive hematopoiesis arises from the ventral wall of dorsal aorta and moves to the caudal hematopoietic tissues, thence the kidney, where life-long and multi-lineage differentiation occurs. The chemical screening platform comprises O-dianisidine staining for hemoglobin containing cells (erythroid) during primitive hematopoiesis. Positive hits were validated based on flow cytometry of dissociated transgenic Tg(gata1:GFP) embryos and whole-mount in-situ hybridization (WISH) for hematopoietic genes. Gene knock-down was conducted by morpholinos (MO) injected into zebrafish embryos at 1-4 cell stage and the effects on hematopoietic development evaluated by WISH and quantitative real-time PCR. Chemical screening of 74 compounds has been performed. These compounds were obtained from a chemical library comprising 879 compounds from NIH (National Institutes of Health) and pre-screened by their effects on cancer cell lines. Four compounds (Tin(IV), chlorotriphenyl [1-(4-ethoxyphenyl)- 3-cyanoureato]-hydrogen,triethylamine, Nogamycin, N,N-Dibenzyldaunorubicin hydrochloride and Allyl 2,3,4-tri-O-benzyl-6-O-(tert-butyldimethylsilyl)-α- D-gluco-Pyranoside) which significantly reduced O-dianisidine staining were identified of which one (Allyl 2,3,4-tri-O-benzyl-6-O-(tert-butyldimethylsilyl) -α-D-glucopyranoside was shown to reduce GFP+ population in Tg(gata1:GFP) population Another chemical (2-Propanol,1,1'-[(1-methylethylidene)bis(4, 1-phenyleneoxy)]bis[3-[(1,1,3,3-tetramethylbutyl)amino]-,dihydrochloride]) was shown to reduce c-myb (marker of definitive hematopoiesis) expression in the ventral wall of dorsal aorta. I also attempted gene knock in zebrafish embryos based on anti-sense morpholino microinjection. A gene encoding for arl4ab was examined, as it was shown to be expressed in hematopoietic tissue in zebrafish embryos but its function is entirely unknown. Knock-down of arl4ab significantly reduced c-myb and runx1 expression in the ventral wall of dorsal aorta and it can be reversed by co-injecting arl4ab mRNA. scl and gata1 expression as well as GFP expression in transgenic Tg(flk1:GFP) embryos that represented vascular development was unaffected. In summary, a zebrafish platform for the study of chemical and genetic modifiers was established. The results have provided important leads for further study into the mechanisms whereby these modifiers regulate…

Subjects/Keywords: Hematopoiesis - Genetics.; Zebra danios as laboratory animals.

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

APA (6^th Edition):

Man, H. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Masters Thesis). University of Hong Kong. Retrieved from Man, H. [文漢威]. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4777052 ; http://dx.doi.org/10.5353/th_b4777052 ; http://hdl.handle.net/10722/174500

Chicago Manual of Style (16^th Edition):

Man, Hon-wai. “A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4).” 2011. Masters Thesis, University of Hong Kong. Accessed December 11, 2019. Man, H. [文漢威]. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4777052 ; http://dx.doi.org/10.5353/th_b4777052 ; http://hdl.handle.net/10722/174500.

MLA Handbook (7^th Edition):

Man, Hon-wai. “A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4).” 2011. Web. 11 Dec 2019.

Vancouver:

Man H. A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). [Internet] [Masters thesis]. University of Hong Kong; 2011. [cited 2019 Dec 11]. Available from: Man, H. [文漢威]. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4777052 ; http://dx.doi.org/10.5353/th_b4777052 ; http://hdl.handle.net/10722/174500.

Council of Science Editors:

Man H. A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). [Masters Thesis]. University of Hong Kong; 2011. Available from: Man, H. [文漢威]. (2011). A study of zebrafish hematopoiesis based on chemical screening and gene knock-down by morpholino with particular reference to ADP-ribosylation factor like 4 (ARL4). (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4777052 ; http://dx.doi.org/10.5353/th_b4777052 ; http://hdl.handle.net/10722/174500

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: 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 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 December 11, 2019. 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. 11 Dec 2019.

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 2019 Dec 11]. Available from: 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: 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 Hong Kong

30. 石祥国; Shi, Xiangguo. Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia.

Degree: PhD, 2015, University of Hong Kong

URL: Shi, X. [石祥国]. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5610968 ; http://hdl.handle.net/10722/221207

► Isocitrate dehydrogenase (IDH) is involved in tricarboxylic acid (TCA) cycle by converting isocitrate to α-ketoglutarate (α-KG) in physiological condition. Recently, recurrent mutations of the IDH1/2… (more)

▼ Isocitrate dehydrogenase (IDH) is involved in tricarboxylic acid (TCA) cycle by converting isocitrate to α-ketoglutarate (α-KG) in physiological condition. Recently, recurrent mutations of the IDH1/2 have been identified in a variety of cancers, including up to 30% of cytogenetically normal acute myeloid leukemia (CN-AML). IDH1/2 mutations confer new metabolic function to the mutant enzymes that catalyze conversion of α-KG to 2-hydroxyglutarate (2-HG). The latter was thought to inhibit α-KG-dependent dioxygenases, including ten-eleven translocation 2 (TET2) and disrupt the epigenetic regulatory network that normally keeps leukemia initiation in check. Zebrafish has emerged as a model organism for the study of hematopoiesis and human diseases and zebrafish IDH1/2 (zidh1/2) are true orthologs of mammalian IDH1/2. In the present study, we investigated the role of zidh1 in embryonic and adult hematopoiesis and evaluated its pathogenetic and therapeutic relevance to human AML. In adult zebrafish, zidh1 was preferentially expressed in the kidney, the equivalence of human bone marrow. During early embryogenesis, it was first ubiquitously expressed and later around the regions of ventral wall of dorsal aorta (DA) and the caudal hematopoietic tissue (CHT), the sites of definitive hematopoiesis. Morpholino knock-down of zidh1 induced differentiation block of primitive myelopoiesis, characterized by an increase in gene expression associated with early myeloid progenitor (pu.1) and decrease in those associated with late myelomonocytic differentiation (l-plastin, mpeg1 and mpo). Definitive hematopoiesis was also reduced, as shown by the down-regulation of c-myb and runx1 along the ventral wall of DA and T-cell marker rag1 in the thymus. To validate our observations, we constructed a TALEN pair targeting exon 1 of zidh1 and injected the TALEN mRNAs into zygotic stage embryos. The efficiency of inducing small insertions or deletions (indels) was 98.7􀁲1.5%. The mutant embryos exhibited defective primitive myelopoiesis and definitive hematopoiesis. Mutant adult fish exhibited an increase in hematopoietic precursor cells in the kidney marrow. Morpholino knock-down of zidh2 also resulted in a blockade of myeloid differentiation as evidenced by increased expression associated with early myeloid progenitor (pu.1) and decreased expression associated with late myelomonocytic differentiation (mpo and l-plastin). Definitive hematopoiesis was not affected. Co-injecting zidh2 mRNA with zidh1 morpholino could not rescue the hematopoietic defects of the latter, indicating non-redundant functions of zidh1 and zidh2. To examine whether the leukemogenic mechanisms of human IDH1-R132H is conserved in zebrafish, we microinjected human IDH1-R132H cDNA into zygotic stage embryos. There was significant increase in 2-HG, associated with increased expression of pu.1, l-plastin, mpeg1 and mpo. The response could be ameliorated by an IDH1-R132H specific inhibitor (AGI-5198). Overexpression of a zebrafish orthologue zidh1-R146H significantly…

Subjects/Keywords: Acute myeloid leukemia; Zebra danio - Genetics; Hematopoiesis

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APA (6^th Edition):

石祥国; Shi, X. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Doctoral Dissertation). University of Hong Kong. Retrieved from Shi, X. [石祥国]. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5610968 ; http://hdl.handle.net/10722/221207

Chicago Manual of Style (16^th Edition):

石祥国; Shi, Xiangguo. “Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia.” 2015. Doctoral Dissertation, University of Hong Kong. Accessed December 11, 2019. Shi, X. [石祥国]. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5610968 ; http://hdl.handle.net/10722/221207.

MLA Handbook (7^th Edition):

石祥国; Shi, Xiangguo. “Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia.” 2015. Web. 11 Dec 2019.

Vancouver:

石祥国; Shi X. Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. [Internet] [Doctoral dissertation]. University of Hong Kong; 2015. [cited 2019 Dec 11]. Available from: Shi, X. [石祥国]. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5610968 ; http://hdl.handle.net/10722/221207.

Council of Science Editors:

石祥国; Shi X. Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. [Doctoral Dissertation]. University of Hong Kong; 2015. Available from: Shi, X. [石祥国]. (2015). Functions of IDH1 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5610968 ; http://hdl.handle.net/10722/221207

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