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University of Hong Kong
1.
Robles, Joseph Delano.
Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study.
Degree: PhD, 2014, University of Hong Kong
URL: Robles,
J.
D..
(2014).
Exploring
the
complications
of
hematopoietic
stem
cell
transplantation
:
a
laboratory
and
clinical
study.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b5435625 
;
http://dx.doi.org/10.5353/th_b5435625
;
http://hdl.handle.net/10722/222426
► This thesis is comprised of two parts, both exploring complications of hematopoietic stem cell transplantation. The first part investigated the immunosuppressive mechanisms of human mesenchymal…
(more)
▼ This thesis is comprised of two parts, both
exploring complications of hematopoietic stem cell transplantation.
The first part investigated the immunosuppressive mechanisms of
human mesenchymal stromal cells (MSCs) in graft versus host disease
(GVHD) murine models. MSCs have been documented to possess the
capability to suppress proliferation of T lymphocytes which is
implicated in acute GVHD, which accounts for around 20% mortality
amongst matched sibling and matched unrelated transplants (CIBMTR,
2013). A number of mechanisms have been described using in vitro or
in vivo studies either by human MSCs administered to humanized
murine models of GVHD or murine MSCs given to GVHD mice. This part
involved exploration of the various mechanisms of immunosuppression
using human MSCs administered to murine GVHD models and monitoring
GVHD clinical score, survival, donor T cell alloreactivity, homing
of MSCs to lymphoid organs and target organs of GVHD, and their
corresponding histopathologic changes. Elucidation of the role of
chemokine receptors and ligands, members of the ephrin family of
receptors and ligands, inducible nitric oxide synthase and
phosphorylated STAT 5 proteins in the immunosuppressive capacity of
MSCs were also studied. This study attempted to form a coherent
explanation of these mechanisms spanning clinicopathologically and
in terms of the immune response of lymphoid organs and target
tissues of acute GVHD. Apart from these, investigation of some of
the receptors, ligands and soluble mediators reported to be
produced by MSCs and use lymphoid organs and target tissues of GVHD
to test these forming a coherent picture of how MSCs exert
immunosuppression in GVHD in an in vivo setting were performed.
The second part of this thesis involved retrospective studies on
Human Herpes Virus 6 and 7 (HHV-6, HHV-7) and Norovirus infections
in paediatric hematopoietic stem cell transplant recipients. Their
incidence in a tertiary hospital in Hong Kong, profile of patients
affected, predisposing or reactivation risk factors, manifestations
and management options were analysed and discussed. These data may
provide clinicians recommendations when their patients become
infected with these viruses post bone marrow transplantation in the
future.
published_or_final_version
Paediatrics and Adolescent
Medicine
Doctoral
Doctor of Philosophy
Subjects/Keywords: Hematopoietic stem cells - Transplantation
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APA (6th Edition):
Robles, J. D. (2014). Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study. (Doctoral Dissertation). University of Hong Kong. Retrieved from Robles, J. D.. (2014). Exploring the complications of hematopoietic stem cell transplantation : a laboratory and clinical study. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435625 ; http://dx.doi.org/10.5353/th_b5435625 ; http://hdl.handle.net/10722/222426
Chicago Manual of Style (16th Edition):
Robles, Joseph Delano. “Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study.” 2014. Doctoral Dissertation, University of Hong Kong. Accessed February 16, 2020.
Robles, J. D.. (2014). Exploring the complications of hematopoietic stem cell transplantation : a laboratory and clinical study. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435625 ; http://dx.doi.org/10.5353/th_b5435625 ; http://hdl.handle.net/10722/222426.
MLA Handbook (7th Edition):
Robles, Joseph Delano. “Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study.” 2014. Web. 16 Feb 2020.
Vancouver:
Robles JD. Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study. [Internet] [Doctoral dissertation]. University of Hong Kong; 2014. [cited 2020 Feb 16].
Available from: Robles, J. D.. (2014). Exploring the complications of hematopoietic stem cell transplantation : a laboratory and clinical study. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435625 ; http://dx.doi.org/10.5353/th_b5435625 ; http://hdl.handle.net/10722/222426.
Council of Science Editors:
Robles JD. Exploring the complications of hematopoietic stem cell
transplantation : a laboratory and clinical study. [Doctoral Dissertation]. University of Hong Kong; 2014. Available from: Robles, J. D.. (2014). Exploring the complications of hematopoietic stem cell transplantation : a laboratory and clinical study. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5435625 ; http://dx.doi.org/10.5353/th_b5435625 ; http://hdl.handle.net/10722/222426
University of California – Santa Cruz
2.
Calhoun, Susan Elizabeth.
Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking.
Degree: Chemistry, 2016, University of California – Santa Cruz
URL: http://www.escholarship.org/uc/item/1rr243q9
► Although hematopoietic stem cells (HSCs) have been successfully used in transplantation therapies for more than 50 years, we still do not have a complete mechanistic…
(more)
▼ Although hematopoietic stem cells (HSCs) have been successfully used in transplantation therapies for more than 50 years, we still do not have a complete mechanistic understanding of the factors that regulate HSC trafficking and engraftment. Recent findings in the Forsberg lab indicate that the vascular endothelium plays important roles in regulating HSC trafficking into and out of bone marrow niches. We hypothesized that sinusoidal endothelial cells marked by the adhesion molecule VCAM-1 mediate the trafficking of HSCs from blood to bone marrow and from bone marrow to blood. Using in vitro transendothelial migration assays, I show that blocking VCAM-1 on HSCs, using blocking antibodies, significantly impairs the ability of HSCs to migrate through endothelial cell layers. These results suggest that VCAM-1 on HSCs is important for HSC extravasation and provide insight into what may be happening in vivo when HSCs must interact with endothelial cells to migrate into and out of the bone marrow.
Subjects/Keywords: Biology; hematopoietic stem cells
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APA (6th Edition):
Calhoun, S. E. (2016). Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/1rr243q9
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Calhoun, Susan Elizabeth. “Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking.” 2016. Thesis, University of California – Santa Cruz. Accessed February 16, 2020.
http://www.escholarship.org/uc/item/1rr243q9.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Calhoun, Susan Elizabeth. “Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking.” 2016. Web. 16 Feb 2020.
Vancouver:
Calhoun SE. Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking. [Internet] [Thesis]. University of California – Santa Cruz; 2016. [cited 2020 Feb 16].
Available from: http://www.escholarship.org/uc/item/1rr243q9.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Calhoun SE. Investigating how VCAM-1+ sinusoidal endothelial cells regulate hematopoietic stem cell trafficking. [Thesis]. University of California – Santa Cruz; 2016. Available from: http://www.escholarship.org/uc/item/1rr243q9
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Columbia University
3.
Upadhaya, Samik K.
Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State.
Degree: 2019, Columbia University
URL: https://doi.org/10.7916/d8-akaq-p920
► Hematopoietic Stem Cells (HSCs) are rare, self-renewing, and multipotent cells that sustain lifelong production of blood and immune cells. Much of our understanding of hematopoiesis,…
(more)
▼ Hematopoietic Stem Cells (HSCs) are rare, self-renewing, and multipotent cells that sustain lifelong production of blood and immune cells. Much of our understanding of hematopoiesis, including the process of divergence and commitment into specific lineages during differentiation, is derived from the analysis of static composition of HSC and progenitor compartments as well as the measurement of their potential using transplantation-based studies. As such, the dynamics of endogenous HSCs, including the kinetics of their differentiation and their interactions with the bone marrow (BM) niche in real-time is poorly understood. The current study aims to characterize HSCs in their native, unperturbed environment by using inducible lineage tracing in combination with high-dimensional flow cytometry and single cell transcriptomics. Our findings provide an unbiased kinetic roadmap of early steps of hematopoietic differentiation and reveal fundamental differences in the sequence of lineage emergence from HSCs. We found a rapid and preferential emergence of megakaryocytic lineage followed by erythroid and myeloid lineages, whereas a substantial delay in lymphopoiesis at steady state. We also used intravital microscopy to visualize endogenous HSCs in the BM of live animals and discovered them to undergo short-range directional movements with extensive morphological changes. Furthermore, our findings revealed profound changes in HSC behavior following treatment with drugs that are used to induce their mobilization into peripheral blood. Overall, the present study offers novel insights into the fundamental features of endogenous HSC differentiation and their in-vivo dynamics during steady state.
Subjects/Keywords: Immunology; Biology; Hematopoietic stem cells
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APA (6th Edition):
Upadhaya, S. K. (2019). Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-akaq-p920
Chicago Manual of Style (16th Edition):
Upadhaya, Samik K. “Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State.” 2019. Doctoral Dissertation, Columbia University. Accessed February 16, 2020.
https://doi.org/10.7916/d8-akaq-p920.
MLA Handbook (7th Edition):
Upadhaya, Samik K. “Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State.” 2019. Web. 16 Feb 2020.
Vancouver:
Upadhaya SK. Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State. [Internet] [Doctoral dissertation]. Columbia University; 2019. [cited 2020 Feb 16].
Available from: https://doi.org/10.7916/d8-akaq-p920.
Council of Science Editors:
Upadhaya SK. Characterization of Endogenous Hematopoietic Stem Cells in Their Native Unperturbed State. [Doctoral Dissertation]. Columbia University; 2019. Available from: https://doi.org/10.7916/d8-akaq-p920
Cape Peninsula University of Technology
4.
Barennise, Arries.
Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
.
Degree: 2017, Cape Peninsula University of Technology
URL: http://etd.cput.ac.za/handle/20.500.11838/2880
► Stem cell transplantation has become one of the standard methods of treatment for patients with malignant and benign blood disorders. The multidisciplinary team interacting with…
(more)
▼ Stem cell transplantation has become one of the standard methods of treatment for patients with malignant and benign blood disorders. The multidisciplinary team interacting with these patients and their families, must be knowledgeable concerning the appropriate quality health care. The objectives of the study were to explore the knowledge of the members of the health care team in terms of the processes that need to be adhered to with
stem cells transplantation, as well as exploring the perceptions amongst the health care team members and their reactions towards patients undergoing
stem cell transplantation. An exploratory research design with a qualitative approach was employed. Data collection took place at two
stem cell transplant units in the Western Cape, using non-probability purposive sampling technique. The health care team members included a medical doctor, dietician, physiotherapist, social worker, radiographer and nursing staff. Data was collected by face-to-face personal interviews which were transcribed and analysed by using coding and thematic analysis. The majority of the professional participants could identify the processes for
stem cell transplantation, which affirmed their knowledge. The non-professional health care team member, could also identify the types of methods and processes of
stem cell transplantation. Participants stated that the health care team members had passion for this treatment option. Some participants felt it to be emotionally challenging to work in the environment, especially with paediatric patients and the dying. However, some health care team members could detach themselves emotionally from the patients. The team stated that the
stem cell transplanted patients need special care to overcome all challenges experienced, but were positive about treatment. It is evident that management of
stem cell transplanted patients is complicated and the health care team members must have knowledge, skills and the appropriate attitude to practice in these units. This study emphasised how vital it is that
stem cell transplantation be included in the training programs of the multidisciplinary team. Health care practitioners in the field must stay abreast with
stem cell research in order to effectively conduct health promotions for patients and staff. In addition, hematology and transplant awareness campaigns should also be conducted in order to educate society and suggest referrals if necessary.
Advisors/Committee Members: Vember, Hilda, Dr (advisor).
Subjects/Keywords: Stem cells;
Stem cells – Transplantation;
Hematopoietic stem cells;
Hematopoietic stem cell disorders – Treatment
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APA (6th Edition):
Barennise, A. (2017). Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
. (Thesis). Cape Peninsula University of Technology. Retrieved from http://etd.cput.ac.za/handle/20.500.11838/2880
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Barennise, Arries. “Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
.” 2017. Thesis, Cape Peninsula University of Technology. Accessed February 16, 2020.
http://etd.cput.ac.za/handle/20.500.11838/2880.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Barennise, Arries. “Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
.” 2017. Web. 16 Feb 2020.
Vancouver:
Barennise A. Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
. [Internet] [Thesis]. Cape Peninsula University of Technology; 2017. [cited 2020 Feb 16].
Available from: http://etd.cput.ac.za/handle/20.500.11838/2880.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Barennise A. Knowledge, perceptions and practices of members of the health care team involved in stem cell transplantations in the Western Cape
. [Thesis]. Cape Peninsula University of Technology; 2017. Available from: http://etd.cput.ac.za/handle/20.500.11838/2880
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universiteit Utrecht
5.
Kolijn, K.
The origin and future of hematopoietic stem cells.
Degree: 2012, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/238606
► Hematopoietic stem cell (HSCs) therapy in the form of bone marrow transplantations has been used successfully in the clinic for over 40 years and continues…
(more)
▼ Hematopoietic stem cell (HSCs) therapy in the form of bone marrow transplantations has been used
successfully in the clinic for over 40 years and continues to save lives daily. Clinical
stem cell
transplantations are required to reconstitute the
hematopoietic system of cancer patients that have
undergone chemotherapy and/or irradiation. Nevertheless, there are still many obstacles with the
clinical use of HSCs, including limited availability of transplantable HSCs, donor matching and graft
versus host reaction and the difficulty to expand HSCs in vitro. Embryonic
stem cells (ESCs) and/or
induced pluripotent
stem cells (iPSCs) could offer a solution to this problem by providing a means to
generate HSCs in vitro. The knowledge to achieve this will likely come from our understanding of the
origin of HSCs in the embryo. In this review, I will discuss the ontogeny of HSCs and the prospects of
using ESCs and/or iPSCs to generate HSCs.
Advisors/Committee Members: Geijsen, Dr. N.
Subjects/Keywords: Hematopoietic stem cells; embryonic stem cells; induced pluripotent stem cells; ontogeny
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APA (6th Edition):
Kolijn, K. (2012). The origin and future of hematopoietic stem cells. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/238606
Chicago Manual of Style (16th Edition):
Kolijn, K. “The origin and future of hematopoietic stem cells.” 2012. Masters Thesis, Universiteit Utrecht. Accessed February 16, 2020.
http://dspace.library.uu.nl:8080/handle/1874/238606.
MLA Handbook (7th Edition):
Kolijn, K. “The origin and future of hematopoietic stem cells.” 2012. Web. 16 Feb 2020.
Vancouver:
Kolijn K. The origin and future of hematopoietic stem cells. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2020 Feb 16].
Available from: http://dspace.library.uu.nl:8080/handle/1874/238606.
Council of Science Editors:
Kolijn K. The origin and future of hematopoietic stem cells. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/238606
IUPUI
6.
Rohrabaugh, Sara L.
Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function.
Degree: 2011, IUPUI
URL: http://hdl.handle.net/1805/2599
► Indiana University-Purdue University Indianapolis (IUPUI)
Cell cycle checkpoints guarantee movement through the cell cycle in an appropriate manner. The spindle assembly checkpoint (SAC) ensures the…
(more)
▼ Indiana University-Purdue University Indianapolis (IUPUI)
Cell cycle checkpoints guarantee movement through the cell cycle in an appropriate manner. The spindle assembly checkpoint (SAC) ensures the proper segregation of chromosomes into daughter cells during mitosis. Mitotic arrest deficiency 2 (Mad2), a member of the mitotic checkpoint proteins, appears to be crucial for generating the wait anaphase signal to prevent onset of anaphase. We first studied the SAC in hematopoietic stem cells (HSC) to ensure that it was functional. Our previous studies found that prolonged SAC activation was uncoupled from apoptosis initiation in mouse and human embryonic stem cells (ESC). We found that upon treatment with a microtubule-destabilizing agent, HSC arrested in M-phase and subsequently initiated apoptosis. Thus unlike ESC, HSC exhibit coupling of prolonged SAC activation with apoptosis. We studied the effects of Mad2+/- on in vivo recovery of bone marrow HPC from cytotoxic effects and also effects of cytostatic agents on HPC growth in vitro using Mad2-haploinsufficient (Mad2+/-) mice. We found that Mad2+/- HPCs were protected from the cytotoxic effects of cytarabine (Ara-C), a cycle specific agent, consistent with Mad2+/- HPCs being in a slow or non-cycling state. Mad2 haploinsufficiency did not affect recovery of functional HPC after treatment with cyclophosphamide or high sub-lethal dose irradiation, both non-cycle specific agents. There were no differences in immunophenotype defined HSCs in Mad2+/- and Mad2+/+ mice, data confirmed by functional HSC competitive repopulation assays. To better understand the role of Mad2 in HPC, E3330, a cytostatic agent, was used to assess the redox function of Ape1/Ref-1, and colony formation in vitro was examined under normoxic and lowered O2 tension. Mad2+/- HPCs were less responsive to E3330 than Mad2+/+ HPCs, and E3330 was more effective under lowered O2 tension. Mad2+/- HPCs did not exhibit enhanced growth in lowered oxygen tension, in contrast to Mad2+/+ HPCs. Our studies have unexpectedly found that Mad2 haploinsufficiency is protective from the cytotoxic effects of a cycle specific DNA synthesis agent in vivo, and Ape1/Ref-1 inhibitor in vitro.
Advisors/Committee Members: Broxmeyer, Hal E., Pelus, Louis, Roman, Ann, Yoder, Mervin C..
Subjects/Keywords: hematopoietic stem cell, hematopoietic progenitor cell, cell cycle; Hematopoietic stem cells; Cell cycle – Regulation
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APA (6th Edition):
Rohrabaugh, S. L. (2011). Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function. (Thesis). IUPUI. Retrieved from http://hdl.handle.net/1805/2599
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rohrabaugh, Sara L. “Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function.” 2011. Thesis, IUPUI. Accessed February 16, 2020.
http://hdl.handle.net/1805/2599.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rohrabaugh, Sara L. “Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function.” 2011. Web. 16 Feb 2020.
Vancouver:
Rohrabaugh SL. Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function. [Internet] [Thesis]. IUPUI; 2011. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/1805/2599.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rohrabaugh SL. Effects of Altering Cell Proliferation on Hematopoietic Stem and Progenitor Cell Function. [Thesis]. IUPUI; 2011. Available from: http://hdl.handle.net/1805/2599
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Utah
7.
Pohlmann, Suzanne Jean.
Engraftment of hematopoietic stem cell and progenitor cell populations;.
Degree: MS;, Oncological Sciences;, 1999, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/841/rec/450
► Bone marrow transplantation has revolutionized human medicine by extending the life span, and even curing, individuals afflicted with cancer and other pathological hematologic conditions. However,…
(more)
▼ Bone marrow transplantation has revolutionized human medicine by extending the life span, and even curing, individuals afflicted with cancer and other pathological hematologic conditions. However, the mechanisms that mediate the engraftment of hematopoietic stem cells (HSCs) after transplantation remain largely obscure. A more comprehensive understanding of the factors that positively and negatively effect engraftment of stem cell and progenitor cell populations is needed to achieve greater success in performing bone marrow and stem cell transplants by preventing the occasional transplant failure. Evaluating the ability of several defined stem cell and progenitor cell populations to contribute to WBC recovery following transplantation into irradiated mice, we found the Rholow subset of stem cells to be solely responsible for bone marrow reconstitution at long periods of time posttransplant. In addition, we identified a lymphoid progenitor cell population that possessed a phenotype very similar to stem cells cells (Sca-1+ c-kit+ Lineageneg Thyneg) and that mediated lymphoid reconstitution of the bone marrow and blood at very early times posttransplant. The results of these studies also demonstrated that the use of different selection protocols for isolating the Thyneg population could drastically diminish the early reconstitutive properties of these cells. Specifically, the c-kit allophycocyanin conjugate derived from the 2B8 clone, but not the c-kit biotin conjugate derived from the ACK4 clone, suppressed the early lymphoid recovery demonstrated by this cell population. Lastly, we devised a new murine model for performing bone marrow transplants that involved transplanting two bone marrow grafts separated by a time interval of several days. Subsequent serial transplantation of bone marrow from reconstituted recipients resulted in significantly greater peripheral blood reconstitution by the second graft in tertiary recipients. However, this was only found to be true when the second graft was administered to primary recipients 3 or 5 days after the first graft. We subsequently revealed there was a 4-fold increase in HSC numbers in primary recipients that received the second graft after a 5-day delay. This supports the idea that HSCs may lose their self-renewal and proliferative properties following transplantation. Therefore, this modified transplant regime may prove useful in preventing graft failure after very long periods of time posttransplant.
Subjects/Keywords: Hematopoietic Stem Cells
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APA (6th Edition):
Pohlmann, S. J. (1999). Engraftment of hematopoietic stem cell and progenitor cell populations;. (Masters Thesis). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/841/rec/450
Chicago Manual of Style (16th Edition):
Pohlmann, Suzanne Jean. “Engraftment of hematopoietic stem cell and progenitor cell populations;.” 1999. Masters Thesis, University of Utah. Accessed February 16, 2020.
http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/841/rec/450.
MLA Handbook (7th Edition):
Pohlmann, Suzanne Jean. “Engraftment of hematopoietic stem cell and progenitor cell populations;.” 1999. Web. 16 Feb 2020.
Vancouver:
Pohlmann SJ. Engraftment of hematopoietic stem cell and progenitor cell populations;. [Internet] [Masters thesis]. University of Utah; 1999. [cited 2020 Feb 16].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/841/rec/450.
Council of Science Editors:
Pohlmann SJ. Engraftment of hematopoietic stem cell and progenitor cell populations;. [Masters Thesis]. University of Utah; 1999. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/841/rec/450
8.
Hinge, Ashwini S.
Studies on the effects of plant lectins on hematopoietic
stem cells.
Degree: 2009, University of Pune
URL: http://shodhganga.inflibnet.ac.in/handle/10603/2550
► Epidemiological studies have shown that the diets rich in fruits, herbs and spices are associated with good health and low risk of cardiovascular disease and…
(more)
▼ Epidemiological studies have shown that the diets
rich in fruits, herbs and spices are associated with good health
and low risk of cardiovascular disease and these foods are rich in
lectins. After ingestion, most lectins bind to the absorptive
microvilli of the small intestine, and from there they may gain
access into the circulation through endocytosis, ultimately
reaching various tissues. The resistance of the lectins towards the
proteolytic activities of digestive enzymes and their ability to
enter systemic circulation and tissues, taken together with their
ability to bind to cell surface molecules containing specific
carbohydrate moieties, indicate that they may affect the functions
of various tissues. Accordingly, it is of considerable importance
to establish whether a given lectin has deleterious or beneficial
effects for mammals. In the present study, we have made a
systematic attempt to examine the effects of two mannose-specific
plant lectins namely, banana lectin (BL) and garlic lectin (GL), on
the hematopoietic stem/progenitor cells. Since both BL and GL are
the constituents of commonly consumed food items – banana and
Garlic – it was imperative to study the effect of an oral
administration of these lectins on the hematopoiesis of mice. The
mice were fed with the lectins on weekly basis for various time
periods and their marrow cells were subjected to stem cell-specific
functional and phenotypic assays. The output of these various
assays clearly indicated that an oral administration of both BL and
GL leads to an increase in the hematopoietic stem/progenitor (HSPC)
pool of the mice.
References p. 146-178, appendices p.
179-197
Advisors/Committee Members: Kale, V P.
Subjects/Keywords: Plant lectins; Hematopoietic stem cells; Cell Sciences
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APA (6th Edition):
Hinge, A. S. (2009). Studies on the effects of plant lectins on hematopoietic
stem cells. (Thesis). University of Pune. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/2550
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hinge, Ashwini S. “Studies on the effects of plant lectins on hematopoietic
stem cells.” 2009. Thesis, University of Pune. Accessed February 16, 2020.
http://shodhganga.inflibnet.ac.in/handle/10603/2550.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hinge, Ashwini S. “Studies on the effects of plant lectins on hematopoietic
stem cells.” 2009. Web. 16 Feb 2020.
Vancouver:
Hinge AS. Studies on the effects of plant lectins on hematopoietic
stem cells. [Internet] [Thesis]. University of Pune; 2009. [cited 2020 Feb 16].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2550.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hinge AS. Studies on the effects of plant lectins on hematopoietic
stem cells. [Thesis]. University of Pune; 2009. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/2550
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of British Columbia
9.
Sutherland, Heather Jeanine.
Purification and characterization of the human hemopoietic stem cell
.
Degree: 1991, University of British Columbia
URL: http://hdl.handle.net/2429/32010
► Previous studies in mice have suggested that some if not all hemopoietic stem cells with long-term in vivo repopulating ability are biologically, physically, and pharmacologically…
(more)
▼ Previous studies in mice have suggested that some if not all hemopoietic stem cells with long-term in vivo repopulating ability are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays. Since human hemopoietic stem cells cannot be assessed by expression of their in vivo repopulating potential, characterization of these cells requires an alternative endpoint. This thesis explores the use of clonogenic cell production in vitro in the presence of a competent stromal cell feeder layer for this purpose, based on the observation that this can continue for many weeks when unseparated human marrow cells are cultured under conditions that allow a stromal cell layer to form. Accordingly, a population of human clonogenic cell precursors referred to as long-term culture-initiating cells (LTC-IC) were postulated to exist as a biologically distinct compartment whose members could be quantitated by measuring the number of myeloid, erythroid and multi-lineage clonogenic progenitors present after 5 weeks of their culture on stromal feeder layers.
LTC-IC in normal marrow assayed in this way were found to have a significantly lower forward light scatter, lower expression of HLA-DR, lower expression of CD 71 (transferrin receptor), and a higher expression of CD 34 as compared to clonogenic cells. Separation of marrow cells on the basis of these differences allowed a cell population enriched ~800 fold in LTC-IC to be obtained. This population contained only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retained 50 - 60% of the LTC-IC present in the original marrow.
Absolute numbers of LTC-IC and the proliferative and differentiative capability of individual LTC-IC were then determined by limiting dilution analysis following the demonstration that clonogenic cell output (at 5 weeks) is linearly related to input cell number over a wide range of cell concentrations. The frequency of LTC-IC in normal human marrow was determined to be ~1 per 2 x 10⁴ cells. Following purification this was increased to 1-2%. The proliferative capacity exhibited by individual LTC-IC as measured by the number of
clonogenic cells per LTC-IC in 5 week-old cultures was found to range from 1 to 30 (the average being ~4). These studies also showed that a least some LTC-IC are multipotent as evident by their production of both erythroid and myeloid progeny.
To study the effect of specific growth factors on LTC-IC maintenance and differentiation, highly purified LTC-IC were seeded onto irradiated murine marrow-derived stromal cells (from the M2-10B4 line) previously engineered to produce one of the human hemopoietic growth factors G-CSF, GM-CSF or IL-3. In the absence of any feeders, both the LTC-IC and their progeny in these purified suspensions decreased to very low levels within 5 weeks. However, in the presence of control M2-10B4 cells, LTC-IC maintenance and differentiation was supported as effectively as when standard human marrow feeders were present. The combined presence of G-CSF…
Subjects/Keywords: Hematopoietic stem cells
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APA (6th Edition):
Sutherland, H. J. (1991). Purification and characterization of the human hemopoietic stem cell
. (Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/32010
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sutherland, Heather Jeanine. “Purification and characterization of the human hemopoietic stem cell
.” 1991. Thesis, University of British Columbia. Accessed February 16, 2020.
http://hdl.handle.net/2429/32010.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sutherland, Heather Jeanine. “Purification and characterization of the human hemopoietic stem cell
.” 1991. Web. 16 Feb 2020.
Vancouver:
Sutherland HJ. Purification and characterization of the human hemopoietic stem cell
. [Internet] [Thesis]. University of British Columbia; 1991. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2429/32010.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sutherland HJ. Purification and characterization of the human hemopoietic stem cell
. [Thesis]. University of British Columbia; 1991. Available from: http://hdl.handle.net/2429/32010
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Cambridge
10.
Ewels, Philip Andrew.
Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells.
Degree: PhD, 2013, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/245861
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608179
► The eukaryotic cell nucleus is a highly organised organelle, with distinct specialised sub- compartments responsible for specific nuclear functions. Within the context of this functional…
(more)
▼ The eukaryotic cell nucleus is a highly organised organelle, with distinct specialised sub- compartments responsible for specific nuclear functions. Within the context of this functional framework, the genome is organised, allowing contact between specific genomic regions and sub-compartments. Previous work has shown that genes in both cis and trans can make specific contacts with each other. I hypothesise that such a preferred juxtaposition may impact the propensity for specific cancerinitiating chromosomal translocations to occur. In this thesis, I describe how I have extended and developed a ligation based proximity assay known as enriched 4C. I have coupled this technique with high throughput sequencing to determine genomic regions that spatially co-associate with the proto-oncogenes MLL, ABL1 and BCR. In addition to further developing the laboratory protocol, I have created bioinformatics tools used in the analysis of the sequencing data. I find that the association profiles of the three genes show strong correlation to the binding profile of RNA polymerase II and other active marks, suggesting that transcribed genes have a propensity to associate with other transcribed regions of the genome. Each gene also exhibits a unique repertoire of preferred associations with specific regions of the genome. Significantly, I find that the most frequent trans association of BCR is telomeric chromosome 9, encompassing its recurrent translocation partner gene ABL1. Interestingly, ABL1 is not at the maximum point of interaction. I use DNA-fluorescence in-situ hybridisation to validate the e4C association. My data supports a hypothesis that gene transcription has a direct role on genome organisation. I suggest that preferred co-associations of genes at transcription factories may promote the occurrence of specific chromosomal translocations.
Subjects/Keywords: 572.8; Proto-oncogenes; Hematopoietic stem cells
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APA (6th Edition):
Ewels, P. A. (2013). Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/245861 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608179
Chicago Manual of Style (16th Edition):
Ewels, Philip Andrew. “Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells.” 2013. Doctoral Dissertation, University of Cambridge. Accessed February 16, 2020.
https://www.repository.cam.ac.uk/handle/1810/245861 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608179.
MLA Handbook (7th Edition):
Ewels, Philip Andrew. “Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells.” 2013. Web. 16 Feb 2020.
Vancouver:
Ewels PA. Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells. [Internet] [Doctoral dissertation]. University of Cambridge; 2013. [cited 2020 Feb 16].
Available from: https://www.repository.cam.ac.uk/handle/1810/245861 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608179.
Council of Science Editors:
Ewels PA. Spatial organisation of proto-oncogenes in human haematopoietic progenitor cells. [Doctoral Dissertation]. University of Cambridge; 2013. Available from: https://www.repository.cam.ac.uk/handle/1810/245861 ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608179
Columbia University
11.
Justino Lage de Almeida, Mariana.
Mitochondrial dynamics in hematopoietic stem cells.
Degree: 2019, Columbia University
URL: https://doi.org/10.7916/d8-tesp-kk78
► Hematopoietic stem cells (HSCs) take on the extraordinary role of sustaining life-long production of blood cells. Despite their indisputable therapeutic potential, HSC biology is poorly…
(more)
▼ Hematopoietic stem cells (HSCs) take on the extraordinary role of sustaining life-long production of blood cells. Despite their indisputable therapeutic potential, HSC biology is poorly understood, and the field remains limited by the inability to maintain, expand, or generate HSCs in vitro. The aim of this study was to elucidate a particular gap in our understanding of the organellar cell biology of HSCs, specifically the role and function of the mitochondria. Several signaling pathways and biological processes converge onto the mitochondria, yet these organelles were found to be largely dispensable in HSCs on the basis of their predominantly glycolytic metabolism and reports of low mitochondrial content.
Our studies show that MitoTracker Green (MTG), a frequently used fluorescent dye to measure mitochondrial mass in hematopoietic populations, is effluxed by HSCs resulting in their systematic and deceptive enrichment in the subset of cells with the lowest MTG fluorescence. Using dye-independent methods we discovered that HSCs have elevated mitochondrial content despite their reliance on glycolysis for ATP production. Moreover, mechanisms of mitochondrial quality control and clearance by autophagy appear to be comparatively lower in HSCs than in any other hematopoietic population we analyzed, suggesting HSCs maintain their mitochondria over time.
To investigate the function of mitochondria in HSCs we generated mice with disruption of mitofusins (MFN) 1 and 2. These proteins are key mediators of mitochondrial fusion, a process that in coordination with mitochondrial fission regulates mitochondrial size, number, and function. Mice with deletion of Mfn1 and Mfn2 (DKO) die perinatally, are pale in appearance and their HSCs show complete loss of regenerative capacity. Several processes linked to dysfunctional mitochondrial fusion and known to be tightly regulated in HSCs are altered in these mutants, including mitochondrial morphology, mitochondrial mass, proliferation, and altered metabolism. Interestingly, one allele of Mfn1 is sufficient to rescue the hematopoietic function and lethality of DKO mice, while one allele of Mfn2 only rescues myeloid reconstitution.
Taken together, our findings highlight the importance and complexity of mitochondrial function and dynamics in HSCs and have contributed to the recently increased appreciation of a vital role for mitochondria in HSCs.
Subjects/Keywords: Immunology; Hematopoietic stem cells; Mitochondria; Cytology; Microbiology
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APA ·
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MLA ·
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CSE |
Export
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APA (6th Edition):
Justino Lage de Almeida, M. (2019). Mitochondrial dynamics in hematopoietic stem cells. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-tesp-kk78
Chicago Manual of Style (16th Edition):
Justino Lage de Almeida, Mariana. “Mitochondrial dynamics in hematopoietic stem cells.” 2019. Doctoral Dissertation, Columbia University. Accessed February 16, 2020.
https://doi.org/10.7916/d8-tesp-kk78.
MLA Handbook (7th Edition):
Justino Lage de Almeida, Mariana. “Mitochondrial dynamics in hematopoietic stem cells.” 2019. Web. 16 Feb 2020.
Vancouver:
Justino Lage de Almeida M. Mitochondrial dynamics in hematopoietic stem cells. [Internet] [Doctoral dissertation]. Columbia University; 2019. [cited 2020 Feb 16].
Available from: https://doi.org/10.7916/d8-tesp-kk78.
Council of Science Editors:
Justino Lage de Almeida M. Mitochondrial dynamics in hematopoietic stem cells. [Doctoral Dissertation]. Columbia University; 2019. Available from: https://doi.org/10.7916/d8-tesp-kk78
12.
Bilotkach, Kateryna.
Quest for early hematopoietic stem cell precursors.
Degree: PhD, 2018, University of Edinburgh
URL: http://hdl.handle.net/1842/33056
► The first transplantable hematopoietic stem cells (HSC) arise in the aorta-gonad mesonephros region (AGM) during early stages of embryo development. Specifically, ventral aspect of embryonic…
(more)
▼ The first transplantable hematopoietic stem cells (HSC) arise in the aorta-gonad mesonephros region (AGM) during early stages of embryo development. Specifically, ventral aspect of embryonic dorsal aorta (DA) contains HSC that upon transplantation into irradiated recipients can reconstitute all lineages of the haematopoietic system [Medvinsky et al. 1993; Muller and Medvinsky, 1994; Medvinsky and Dzierzak, 1996; Cumano et al., 1996; Tavian et al., 1996; Peault and Tavian, 2003; Taoudi and Medvinsky, 2007; Ivanovs et al., 2011, 2014]. The ventral aspect of DA bears so-called intra-aortic cell clusters (IAC), the appearance of which coincides with the emergence of HSC [Babovic and Eaves, 2014; Bhatia, 2007; Boisset et al., 2010, 2011; Bollerot et al., 2005; de Bruijin et al., 2002; Bertrand et al., 2010]. According to recent reports, HSC are a heterogeneous population of cells [Dykstra et al., 2007; Seita and Weissman, 2010; Muller-Sieburg et al., 2012]. It is unclear whether all HSC precursors originate from the same location, for example, DA lining, IAC or sub-aortic tissues; or HSC precursors migrate into DA lining from other parts of the embryo [Tavian et al., 1999; Yoder et al., 1997; Oberlin et al., 2002; Peault and Tavian, 2003; Dzierzak, 2003; Samokhvalov et al., 2007; Medvinsky et al., 2011]. To elucidate ontogeny of early HSC precursors (pro-HSC), two approaches were applied in this PhD project. First, we mapped potential pro-HSC in pre-circulation mouse embryos (embryonic day 6-8.5, E6-E8.5). We defined potential pro-HSC as cells co-expressing the transcription factor Runx1, endothelial markers (VE-Cad or CD31) and/or haematopoietic markers (CD45, CD41) [Oberlin et al., 2002; de Bruijn and Dzierzak, 2012; Liakhovitskaia et al., 2009, 2014]. In E6-E8 mouse embryo, prospective pro-HSC were found to be located in chorionic plate, yolk sac and in allantoic core domain. In early somitic mouse embryo (E8-8.5) cells with pro-HSC phenotype (Runx1+CD31+CD41+) were found to be in cell clusters in forming vessel of confluence and in nascent dorsal aortae lining. Pro-HSC are not directly transplantable [Cumano et al., 1996., 2001; Godin et al., 1993; 1995; Batta et al., 2016; Matsuoka et al., 2001; Nishikawa et al., 1998]. Therefore, cells and tissues containing prospective pro-HSC were initially matured using several in-vitro culture systems. According to our results, E8 mouse embryo pro-HSC are only preserved in explant cultures, but not in co-aggregate cultures with stroma cells. After culture, cells were transplanted into sub-lethally irradiated recipients. Six weeks after transplantation 19 out of 82 transplanted recipients had donor derived blood cells' chimerism at the level of 0.1-0.3%. Forty six percent of these grafts were derived from rostral part of the embryo tissues (head, heart, upper somites). Only one out of 82 recipients had donor cells contribution above 1% (1.2 %). This recipient was engrafted with cells derived from the E8 mouse embryo head and heart region. Recipients having blood chimerism at the…
Subjects/Keywords: hematopoietic stem cells; embryonic hematopoiesis; precursors; Runx1
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APA (6th Edition):
Bilotkach, K. (2018). Quest for early hematopoietic stem cell precursors. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/33056
Chicago Manual of Style (16th Edition):
Bilotkach, Kateryna. “Quest for early hematopoietic stem cell precursors.” 2018. Doctoral Dissertation, University of Edinburgh. Accessed February 16, 2020.
http://hdl.handle.net/1842/33056.
MLA Handbook (7th Edition):
Bilotkach, Kateryna. “Quest for early hematopoietic stem cell precursors.” 2018. Web. 16 Feb 2020.
Vancouver:
Bilotkach K. Quest for early hematopoietic stem cell precursors. [Internet] [Doctoral dissertation]. University of Edinburgh; 2018. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/1842/33056.
Council of Science Editors:
Bilotkach K. Quest for early hematopoietic stem cell precursors. [Doctoral Dissertation]. University of Edinburgh; 2018. Available from: http://hdl.handle.net/1842/33056
University of New South Wales
13.
Guan, Yi Fang.
Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG.
Degree: Clinical School - Prince of Wales Hospital, 2017, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/57197
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42784/SOURCE02?view=true
► Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed…
(more)
▼ Aberrant
stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-cell acute lymphoblastic leukaemia (T- ALL) and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic
cells remain poorly understood. In order to discover transcriptional regulators of ERG, I employed a quantitative mass spectrometry (MS)-based method to identify factors binding the ERG +85
stem cell enhancer region in MOLT-4 and KG-1
cells. Using this approach, I identified a number of known transcription factors (TF) bound to the ERG +85 enhancer in leukaemic
cells along with previously unknown binders, ETV6 and IKZF1. I confirmed that ETV6 and IKZF1 were also bound in vivo at the ERG +85 enhancer in both leukaemic
cells and in healthy human CD34+ haematopoietic
stem and progenitor
cells (HSPCs). Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators of ERG and a number of genes regulated by a densely interconnected network of the heptad TF. Furthermore, I showed that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis.Protein phosphorylation is known to regulate the transcriptional activity of genes. Aberrant protein phosphorylation can lead to numerous haematological malignancies, but few studies have focused on phosphorylations of DNA bound TF at regulatory DNA. By adapting the reverseChIP method I develop an approach to identify and quantify of site-specific phosphorylation if TF on DNA in vitro using MOLT-4 and KG-1
cells. I have identified phosphorylated DNA bound TFs and 28 novel phosphorylation sites that are uniquely enriched at the ERG+85 enhancer under a leukaemia context. Oncoprotein ETS1 was identified as exhibiting changes in phosphorylation when bound to DNA compared to the nuclear input, this finding was also validated by western blot.This work significantly expands existing knowledge of the regulation of ERG over-expression driven by the ERG+85 enhancer in leukaemic and HSPCs
cells. In addition, both reverseChIP methods can be utilised to study other regulatory regions of interest.
Advisors/Committee Members: Pimanda , John Eshantha Manil Obeyesekere, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW, Wong, Jason Wing Hon, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW, Unnikrishnan, Ashwin, Clinical School - Prince of Wales Hospital, Faculty of Medicine, UNSW.
Subjects/Keywords: transcriptional network; ERG; hematopoietic stem cells
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APA (6th Edition):
Guan, Y. F. (2017). Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/57197 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42784/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Guan, Yi Fang. “Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG.” 2017. Doctoral Dissertation, University of New South Wales. Accessed February 16, 2020.
http://handle.unsw.edu.au/1959.4/57197 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42784/SOURCE02?view=true.
MLA Handbook (7th Edition):
Guan, Yi Fang. “Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG.” 2017. Web. 16 Feb 2020.
Vancouver:
Guan YF. Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2020 Feb 16].
Available from: http://handle.unsw.edu.au/1959.4/57197 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42784/SOURCE02?view=true.
Council of Science Editors:
Guan YF. Proteomics based approaches to identify DNA binding transcriptional regulators and phosphoproteins of ERG. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/57197 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:42784/SOURCE02?view=true
University of Texas Southwestern Medical Center
14.
Kocabas, Fatih.
MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1251
► Stem cells undergo self-renewal, maintaining themselves in an undifferentiated state while generating differentiated cells that are required for the tissue homeostasis or repair. One intriguing…
(more)
▼ Stem cells undergo self-renewal, maintaining themselves in an undifferentiated state while generating differentiated
cells that are required for the tissue homeostasis or repair. One intriguing feature of
stem cells is their maintenance in their respective hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. However, little is known about
stem cell metabolism, its regulation or its effect on
stem cell function. We started our work by focusing on the most comprehensively characterized adult
stem cell population, the
hematopoietic stem cells (HSCs). We demonstrate that mouse and human HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. Furthermore, we demonstrate that Meis1 and Hif-1α are markedly enriched in HSCs and that Meis1 functions upstream of the two master redox regulators Hif-1α and Hif-2α, where loss of Meis1 results in a metabolic shift from glycolysis to mitochondrial oxidative metabolism, and increased oxidative stress, and loss of HSC quiescence. These results underscore the critical link between metabolism and cell cycle regulation of HSCs. We then sought to determine whether other
stem cell populations share these unique metabolic characteristics. This strategy enabled us to identify the epicardium and the subepicardium of the heart as the cardiac hypoxic
stem cell niche, which houses a metabolically distinct, Hif-1α positive population of glycolytic cardiac progenitors. Moreover, our studies indicate that Meis1, which regulates HSC metabolism and quiescence, also induces post-natal cell cycle exit and quiescence of cardiomyocytes through induction of synergistic cyclin dependent kinase inhibitor families. We demonstrate that both embryonic and adult deletion of Meis1 in cardiomyocytes results in widespread cardiomyocyte proliferation in the adult heart. Overall, our studies identify Meis1 as a critical transcriptional regulator of cell cycle and metabolism.
Advisors/Committee Members: Sadek, Hesham A..
Subjects/Keywords: Neoplasm Proteins; Hematopoietic Stem Cells; Homeodomain Proteins
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APA (6th Edition):
Kocabas, F. (2013). MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1251
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kocabas, Fatih. “MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed February 16, 2020.
http://hdl.handle.net/2152.5/1251.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kocabas, Fatih. “MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation.” 2013. Web. 16 Feb 2020.
Vancouver:
Kocabas F. MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2152.5/1251.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kocabas F. MEIS1: At the Crossroads Between Metabolic and Cell Cycle Regulation. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1251
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
15.
Garcia, Analucia.
Defining the Role of SOX17 in Human Hematopoietic Development.
Degree: 2018, University of Toronto
URL: http://hdl.handle.net/1807/91480
► The transcriptional regulators that govern the generation of hematopoietic stem cells (HSCs) from hemogenic endothelial cells (HECs) during human definitive hematopoiesis have not been identified.…
(more)
▼ The transcriptional regulators that govern the generation of hematopoietic stem cells (HSCs) from hemogenic endothelial cells (HECs) during human definitive hematopoiesis have not been identified. Based on findings from studies in the mouse, we hypothesized that the transcription factor SOX17 plays a pivotal role in the establishment of the definitive, but not the primitive hematopoietic program generated from human pluripotent stem cells (hPSCs) differentiated in culture. We observed that SOX17 was expressed within definitive CD34+ ‘HECs’ and emerging definitive, but not primitive, CD43+ hematopoietic cells. Detailed analyses showed that expression of SOX17 was downregulated as CD34+ HECs differentiate and undergo an endothelial-to-hematopoietic transition (EHT) to acquire a hematopoietic fate. This transition from a SOX17+ to a SOX17– population was blocked using a NOTCH signaling inhibitor. Despite the expression of SOX17 in definitive progenitors, the loss of SOX17 had no effect on definitive or primitive hematopoiesis in the hPSC differentiation cultures.
M.Sc.
Advisors/Committee Members: Keller, Gordon, Medical Biophysics.
Subjects/Keywords: Cell differentiation; Hematopoiesis; Hematopoietic stem cells; Stem cells; Transcription factors; 0758
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APA ·
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Manager
APA (6th Edition):
Garcia, A. (2018). Defining the Role of SOX17 in Human Hematopoietic Development. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/91480
Chicago Manual of Style (16th Edition):
Garcia, Analucia. “Defining the Role of SOX17 in Human Hematopoietic Development.” 2018. Masters Thesis, University of Toronto. Accessed February 16, 2020.
http://hdl.handle.net/1807/91480.
MLA Handbook (7th Edition):
Garcia, Analucia. “Defining the Role of SOX17 in Human Hematopoietic Development.” 2018. Web. 16 Feb 2020.
Vancouver:
Garcia A. Defining the Role of SOX17 in Human Hematopoietic Development. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/1807/91480.
Council of Science Editors:
Garcia A. Defining the Role of SOX17 in Human Hematopoietic Development. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/91480
University of Lund
16.
Jansson, Lina.
Genetic modeling of the Hippo pathway in hematopoietic
stem cells.
Degree: 2012, University of Lund
URL: https://lup.lub.lu.se/record/2370099
;
https://portal.research.lu.se/ws/files/3269912/2370126.pdf
► Hematopoiesis is the process of blood formation from a limited pool of hematopoietic stem cells (HSCs). These rare stem cells can both self-renew to maintain…
(more)
▼ Hematopoiesis is the process of blood formation
from a limited pool of hematopoietic stem cells (HSCs). These rare
stem cells can both self-renew to maintain the HSC pool, and
differentiate to continuously replenish lost blood cells. The
mechanisms of HSC regulation are not fully known. The aim of this
thesis was to study the role of the Hippo signaling pathway in
HSCs. The Hippo pathway is a newly discovered signaling pathway,
which regulates organ size in Drosophila. Hippo signaling has
further been implicated in regulation of mammalian stem cells. In
Article I we developed a new way of modeling genetic changes by
combining genetic engineering of murine ES cells with blastocyst
complementation. This approach avoids the cost and time constraints
associated with the creation of standard transgenic mouse strains
while taking advantage of the sophisticated site-directed
manipulations that are possible in ES cells. In Article II we
studied YAP1, the downstream effector in the Hippo pathway. We
created a transgenic model with inducible YAP1 expression
exclusively within the hematopoietic system using the blastocyst
complementation approach developed in article I. When investigating
the effect of overexpressing YAP1 in HSCs we detected no effect on
HSC function during steady state or regenerative stress. This is
contrast to effects seen in other tissue stem cells and suggests
tissue specific functions of YAP1 in regulation of stem cells. In
Article III we investigated a knockout model for the other Hippo
effector Taz. Adult mice deficient in Taz display no changes in
hematopoietic parameters but are born below mendelian ratios. Taz
thus seems dispensable for adult hematopoiesis but may influence
embryonic development. Taken together, using both novel and
traditional genetic engineering approaches in mice, we have taken
the first steps to understand the role of the Hippo pathway in
hematopoiesis.
Subjects/Keywords: Hematology; stem cells; hematopoiesis; Hippo pathway; hematopoietic stem cells
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APA (6th Edition):
Jansson, L. (2012). Genetic modeling of the Hippo pathway in hematopoietic
stem cells. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/2370099 ; https://portal.research.lu.se/ws/files/3269912/2370126.pdf
Chicago Manual of Style (16th Edition):
Jansson, Lina. “Genetic modeling of the Hippo pathway in hematopoietic
stem cells.” 2012. Doctoral Dissertation, University of Lund. Accessed February 16, 2020.
https://lup.lub.lu.se/record/2370099 ; https://portal.research.lu.se/ws/files/3269912/2370126.pdf.
MLA Handbook (7th Edition):
Jansson, Lina. “Genetic modeling of the Hippo pathway in hematopoietic
stem cells.” 2012. Web. 16 Feb 2020.
Vancouver:
Jansson L. Genetic modeling of the Hippo pathway in hematopoietic
stem cells. [Internet] [Doctoral dissertation]. University of Lund; 2012. [cited 2020 Feb 16].
Available from: https://lup.lub.lu.se/record/2370099 ; https://portal.research.lu.se/ws/files/3269912/2370126.pdf.
Council of Science Editors:
Jansson L. Genetic modeling of the Hippo pathway in hematopoietic
stem cells. [Doctoral Dissertation]. University of Lund; 2012. Available from: https://lup.lub.lu.se/record/2370099 ; https://portal.research.lu.se/ws/files/3269912/2370126.pdf
Hong Kong University of Science and Technology
17.
Li, Xiuling.
SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis.
Degree: 2011, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-7587
;
https://doi.org/10.14711/thesis-b1155413
;
http://repository.ust.hk/ir/bitstream/1783.1-7587/1/th_redirect.html
► Hematopoiesis is a conserved blood generation process in vertebrates, consisting of two blood generation waves: the primitive and the definitive hematopoiesis. One unique feature of…
(more)
▼ Hematopoiesis is a conserved blood generation process in vertebrates, consisting of two blood generation waves: the primitive and the definitive hematopoiesis. One unique feature of the definitive wave is the existence of hematopoietic stem/progenitor cells (HSPCs), which are not present in the primitive wave. In zebrafish, the HSCs originate from the ventral wall of the dorsal aorta (VDA), then migrate to an intermediate hematopoietic niche called causal hematopoietic tissue (CHT) where the HSPCs pools are established. Finally they home to the kidney where the adult hematopoiesis is maintained. Although the ontogeny of HSPCs has been studied extensively, the genetic program specifying its migration, colonization and maintenance is still not fully understood. In this study, we isolated a zebrafish mutant, named tangohkz3, from a forward genetic screening in Ethylnitrosourea (ENU)-treated zebrafishes. By characterizing the phenotype of tangohkz3, the mutant exhibited a defect of definitive HSPCs maintenance in the CHT, as a consequence, all the definitive blood lineages including erythroid, myeloid and lymphoid cells were impaired. Cellular study showed that the HSPCs in CHT exhibited mild increase of apoptosis and obvious decrease of proliferation. Positional cloning and RNA rescue experiment revealed that SUMO1 activating enzyme subunit 1 (sae1) gene, which coded a component of the activating enzyme for sumoylation modification, was responsible for the mutant phenotype. The Q273X mutation of sae1 was proved to cause insufficient sumoylation modification both in vivo in zebrafish and in vitro in cell lines. More over, the sae1 gene was found ubiquitously expressed in the fish embryo, and was cell-autonomously required for the HSPCs maintenance in the mutant. Our study demonstrated that sae1 is essential for the HSPCs development during zebrafish fetal hematopoiesis.
Subjects/Keywords: Hematopoietic growth factors
; Hematopoiesis
; Hematopoietic stem cells
; Zebra danio – Physiology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, X. (2011). SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7587 ; https://doi.org/10.14711/thesis-b1155413 ; http://repository.ust.hk/ir/bitstream/1783.1-7587/1/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 (16th Edition):
Li, Xiuling. “SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed February 16, 2020.
http://repository.ust.hk/ir/Record/1783.1-7587 ; https://doi.org/10.14711/thesis-b1155413 ; http://repository.ust.hk/ir/bitstream/1783.1-7587/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Li, Xiuling. “SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis.” 2011. Web. 16 Feb 2020.
Vancouver:
Li X. SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2020 Feb 16].
Available from: http://repository.ust.hk/ir/Record/1783.1-7587 ; https://doi.org/10.14711/thesis-b1155413 ; http://repository.ust.hk/ir/bitstream/1783.1-7587/1/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:
Li X. SUMO1 activating enzyme subunit 1 is essential for the maintenance of hematopoietic stem/progenitor cells during zebrafish hematopoiesis. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-7587 ; https://doi.org/10.14711/thesis-b1155413 ; http://repository.ust.hk/ir/bitstream/1783.1-7587/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Hong Kong University of Science and Technology
18.
Lan, Yahui.
Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance.
Degree: 2011, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-7616
;
https://doi.org/10.14711/thesis-b1155066
;
http://repository.ust.hk/ir/bitstream/1783.1-7616/1/th_redirect.html
► The establishment of entire blood system relies on the multi-potent hematopoietic stem cells (HSCs), thus identifying the molecular mechanism in HSC generation is of importance…
(more)
▼ The establishment of entire blood system relies on the multi-potent hematopoietic stem cells (HSCs), thus identifying the molecular mechanism in HSC generation is of importance for not only complementing the fundamental knowledge in stem cell biology, but also providing insights to the regenerative therapies. Recent researches have documented the formation of nascent HSCs through a direct transition from ventral aortic endothelium, named as endothelial hematopoietic transition (EHT) process. However, the precise genetic program engaged in this process remains largely elusive. The transcription factor scl plays pivotal and conserved roles in embryonic and adult hematopoiesis from teleosts to mammals. Our lab have previously identified a new truncated scl isoform, scl-β, which is indispensible for the specification of HSCs in the ventral wall of dorsal aorta (VDA), the zebrafish equivalent of mammalian fetal hematopoietic organ. Here we observe that, by combining time-lapse confocal imaging of transgenic zebrafish and genetic epistasis analysis, scl-β is expressed in a subset of ventral aortic endothelial cells and critical for their forthcoming transformation to hemogenic endothelium; in contrast, runx1 is required downstream to govern the successful egress of the hemogenic endothelial cells to become naïve HSCs. In addition, the traditional known full-length scl-α isoform is firstly evidenced to be required for the maintenance or survival of newly formed HSCs in VDA. Collectively our data has established the genetic hierarchy controlling discrete steps in the consecutive process of HSC formation from endothelial cells and further development in VDA.
Subjects/Keywords: Hematopoiesis
; Hematopoietic stem cells
; Hematopoietic growth factors
; Zebra danio – Genetics
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lan, Y. (2011). Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-7616 ; https://doi.org/10.14711/thesis-b1155066 ; http://repository.ust.hk/ir/bitstream/1783.1-7616/1/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 (16th Edition):
Lan, Yahui. “Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance.” 2011. Thesis, Hong Kong University of Science and Technology. Accessed February 16, 2020.
http://repository.ust.hk/ir/Record/1783.1-7616 ; https://doi.org/10.14711/thesis-b1155066 ; http://repository.ust.hk/ir/bitstream/1783.1-7616/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lan, Yahui. “Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance.” 2011. Web. 16 Feb 2020.
Vancouver:
Lan Y. Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2011. [cited 2020 Feb 16].
Available from: http://repository.ust.hk/ir/Record/1783.1-7616 ; https://doi.org/10.14711/thesis-b1155066 ; http://repository.ust.hk/ir/bitstream/1783.1-7616/1/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:
Lan Y. Distinct functions of different scl isoforms in zebrafish definitive hematopoietic stem cell initiation and maintenance. [Thesis]. Hong Kong University of Science and Technology; 2011. Available from: http://repository.ust.hk/ir/Record/1783.1-7616 ; https://doi.org/10.14711/thesis-b1155066 ; http://repository.ust.hk/ir/bitstream/1783.1-7616/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
19.
Parker, Aaron Samuel.
Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines.
Degree: Biology, 2011, University of California – San Diego
URL: http://www.escholarship.org/uc/item/55z05025
► By mimicking embryonic development of the hematopoietic system, we have developed an optimized in vitro differentiation protocol for the generation of precursors of hematopoietic lineages…
(more)
▼ By mimicking embryonic development of the hematopoietic system, we have developed an optimized in vitro differentiation protocol for the generation of precursors of hematopoietic lineages and primitive hematopoietic cells from human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells. Factors such as cytokines, extra cellular matrix components, and small molecules, as well as the temporal association and concentration of these factors were tested on seven different human ES and iPS lines. We report the conversion of up to 84% huCD45+ cells (average 41% ± 16, from 7 pluripotent lines) from the differentiation culture, including significant numbers of primitive CD45+CD34+ and CD45+CD34+CD38- hematopoietic progenitors. Moreover, the numbers of hematopoietic progenitor cells generated, as measured by colony forming unit assays were comparable to numbers obtained from fresh umbilical cord blood mononuclear cell isolates on a per CD45+ cell basis. Our approach demonstrates highly efficient generation of multipotent hematopoietic progenitors with the highest efficiencies reported to date (CD45+/CD34+) using a single standardized differentiation protocol on several human ES and iPS cell lines. Our data add to the cumulating evidence for the existence of an in vitro derived precursor to the hematopoietic stem cell (HSC) with limited engrafting ability in transplanted mice, but with multipotent hematopoietic potential. Because this protocol efficiently expands the pre-blood precursors and hematopoietic progenitors, it is ideal for testing novel factors for the generation and expansion of definitive hematopoietic stem cells with long-term repopulating ability.
Subjects/Keywords: Biology; Blood; Differentiation; Embryonic Stem Cells; Hematopoietic Stem Cells; Pluripotent Stem Cells; Progenitors
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Parker, A. S. (2011). Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/55z05025
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Parker, Aaron Samuel. “Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines.” 2011. Thesis, University of California – San Diego. Accessed February 16, 2020.
http://www.escholarship.org/uc/item/55z05025.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Parker, Aaron Samuel. “Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines.” 2011. Web. 16 Feb 2020.
Vancouver:
Parker AS. Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines. [Internet] [Thesis]. University of California – San Diego; 2011. [cited 2020 Feb 16].
Available from: http://www.escholarship.org/uc/item/55z05025.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Parker AS. Efficient Generation of Hematopoietic Precursors and Progenitors from Human Pluripotent Stem Cell Lines. [Thesis]. University of California – San Diego; 2011. Available from: http://www.escholarship.org/uc/item/55z05025
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
20.
Kim, Seungbum.
In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone.
Degree: PhD, Medical Sciences - Molecular Cell Biology (IDP), 2011, University of Florida
URL: http://ufdc.ufl.edu/UFE0043651
► A fundamental question in stem cell biology is where stem cells reside and how stem cell niches control stem cell activity in vivo. Although the…
(more)
▼ A fundamental question in
stem cell biology is where
stem cells reside and how
stem cell niches control
stem cell activity in vivo. Although the
hematopoietic stem cell (HSC) is well characterized, our current knowledge of where and how transplanted HSPCs become engrafted is very limited. HSC transplantation is now routinely done in clinics to correct a variety of bone marrow deficiencies. Considering its extensive use, understanding the HSPC engraftment process has now become critical if we are to improve the treatment strategies. A key to understanding HSC engraftment is to be able to observe the process in vivo. I aimed to visualize fluorescent HSC in the mouse tibia bone directly by grinding one side of the tibia until the bone was sufficiently thin for direct observation. By making a "window" into the tibia bone, I was able to observe the very early engraftment process of a single HSC lodging and proliferating at the bone marrow niche. The Sca-1+, c-Kit+, Lin- (SKL)
cells preferred to prosper mainly on the osteoblastic niche. In contrast, further purified SKL, CD48-, CD150+ population (SLAM-SKL) was mostly observed in the perivascular niche. When mice were co-transplanted with DsRed+ SKL and GFP+ SLAM-SKL populations, SKL
cells were 25 times more than SLAM-SKL
cells in the bone marrow at Day 7. However, contribution of each population to the blood circulation at the same time was not consistent. It was extramedullary hematopoiesis observed from the spleen that produced extra amount of blood from SLAM-SKL
cells, which suggests that the SLAM-SKL
cells engrafted in the perivascular niche in both BM and spleen and can support hematopoiesis much quicker than SKL
cells. This study shows a novel technique to understand and highlight the dynamic process of the
stem cell engraftment in complex microenvironment of the bone marrow. ( en )
Advisors/Committee Members: Scott, Edward W (committee chair), Grant, Maria A (committee member), Cogle, Christopher Ramin (committee member), Siemann, Dietmar W (committee member).
Subjects/Keywords: Bone marrow; Bones; Cells; Dyes; Hematopoietic stem cells; Imaging; Osteoblasts; Spleen; Stem cells; Tibia; cell – hematopoietic – imaging – stem – transplantation
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APA ·
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Export
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APA (6th Edition):
Kim, S. (2011). In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone. (Doctoral Dissertation). University of Florida. Retrieved from http://ufdc.ufl.edu/UFE0043651
Chicago Manual of Style (16th Edition):
Kim, Seungbum. “In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone.” 2011. Doctoral Dissertation, University of Florida. Accessed February 16, 2020.
http://ufdc.ufl.edu/UFE0043651.
MLA Handbook (7th Edition):
Kim, Seungbum. “In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone.” 2011. Web. 16 Feb 2020.
Vancouver:
Kim S. In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone. [Internet] [Doctoral dissertation]. University of Florida; 2011. [cited 2020 Feb 16].
Available from: http://ufdc.ufl.edu/UFE0043651.
Council of Science Editors:
Kim S. In Vivo Imaging of the Hematopoietic Stem Cell Engraftment Process in the Mouse Tibia Bone. [Doctoral Dissertation]. University of Florida; 2011. Available from: http://ufdc.ufl.edu/UFE0043651
University of Illinois – Urbana-Champaign
21.
Mahadik, Bhushan Prakash P.
Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate.
Degree: MS, 0300, 2011, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/18358
► Hematopoiesis is a physiological process responsible for the generation of all the blood and immune cells of the body. The cells responsible for this process…
(more)
▼ Hematopoiesis is a physiological process responsible for the generation of all the blood and immune
cells of the body. The
cells responsible for this process are the
hematopoietic stem cells (HSCs), primarily located within the bone marrow. They are housed in specific microenvironments (niches) that provide stochastically and temporally mutable signals that influence
stem cell fate of differentiation, quiescence, self-renewal and apoptosis. The niche signals may also contribute to HSC disregulation and
hematopoietic pathologies, notably leukemia
stem cell (LSC) mediated leukemogenesis. The niche consists of several components such as the extracellular matrix (ECM), surrounding niche
cells and several soluble or ECM-bound factors that influence the HSC fate. Critical as the function of the niche seems, surprisingly little is known about these regulatory processes and the mechanisms governing them. This thesis attempts to provide an engineering solution to understanding the complex biological mechanism of HSC-niche cell interaction and its influence on HSC fate. We believe that combinatorial biomaterials can be used to systematically expose discrete populations of HSCs and niche
cells to defined 3D microenvironments; such tools can generate critical information to help decode the interrelationship between extrinsic cues, intracellular signaling networks, and HSC fate.
Advisors/Committee Members: Harley, Brendan A. (advisor).
Subjects/Keywords: Biomaterial; gradient hydrogel; hematopoietic stem cells (HSCs); stem cell fate regulation
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APA ·
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APA (6th Edition):
Mahadik, B. P. P. (2011). Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18358
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mahadik, Bhushan Prakash P. “Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate.” 2011. Thesis, University of Illinois – Urbana-Champaign. Accessed February 16, 2020.
http://hdl.handle.net/2142/18358.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mahadik, Bhushan Prakash P. “Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate.” 2011. Web. 16 Feb 2020.
Vancouver:
Mahadik BPP. Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2011. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2142/18358.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mahadik BPP. Multigradient hydrogels to decode extrinsic regulation of hematopoietic stem cell fate. [Thesis]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18358
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Universiteit Utrecht
22.
Bastiaansen, K.C.J.T.
Wnt signaling in hematopoietic stem cell maintenance.
Degree: 2010, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/187075
► Wnt proteins are known to signal via canonical β-catenin-mediated and non-canonical β-catenin-independent signaling pathways and are involved in various developmental processes. Both Wnt signaling pathways…
(more)
▼ Wnt proteins are known to signal via canonical β-catenin-mediated and non-canonical β-catenin-independent signaling pathways and are involved in various developmental processes. Both Wnt signaling pathways are involved in
hematopoietic stem cell (HSC) maintenance, but how they regulate quiescence, proliferation and differentiation is not yet fully understood. In this thesis, I aim to gain insight in the role of Wnt signaling in HSC regulation.
HSCs have the capacity to self-renew, but can also be induced to differentiate into all
cells of the
hematopoietic compartment. Wnt proteins are secreted by the stromal
cells that make up the bone marrow
stem cell niche, but are also produced by HSCs themselves. Studies on how Wnt signaling relates to HSC function however yielded contrasting results, with the majority of evidence pointing to a role for Wnt signaling in proliferation and self-renewal. Surprisingly, deletion of β-catenin has no effect on HSC maintenance. In contrast, overexpression of β-catenin results in an increase of HSC proliferation, while
stem cells retain an undifferentiated character. Deletion of Wnt3a impairs the self-renewal capacity of HSCs in vivo and consequently, overexpression of Wnt3a results in an increase of proliferation and a block in differentiation. Enforced activation of Wnt signaling pathways, achieved for example by inhibition of GSK-3β or deletion of Apc, results in expansion of the
stem cell pool. Non-canonical Wnt signaling via Wnt5a or Wnt4 induces proliferation or provides a signal for quiescence, depending on the context in which signaling occurs.
Together, Wnt signaling appears to play an essential role in regulation of the
hematopoietic stem cell pool. Most Wnt signaling pathways seem to promote self-renewal, as they induce proliferation and inhibit differentiation of HSCs. Therefore, Wnt signaling is a crucial factor in the maintenance of this adult
stem cell pool.
Advisors/Committee Members: Maurice, Madelon.
Subjects/Keywords: Wnt signaling; hematopoietic stem cells; stem cell niche
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APA ·
Chicago ·
MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bastiaansen, K. C. J. T. (2010). Wnt signaling in hematopoietic stem cell maintenance. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/187075
Chicago Manual of Style (16th Edition):
Bastiaansen, K C J T. “Wnt signaling in hematopoietic stem cell maintenance.” 2010. Masters Thesis, Universiteit Utrecht. Accessed February 16, 2020.
http://dspace.library.uu.nl:8080/handle/1874/187075.
MLA Handbook (7th Edition):
Bastiaansen, K C J T. “Wnt signaling in hematopoietic stem cell maintenance.” 2010. Web. 16 Feb 2020.
Vancouver:
Bastiaansen KCJT. Wnt signaling in hematopoietic stem cell maintenance. [Internet] [Masters thesis]. Universiteit Utrecht; 2010. [cited 2020 Feb 16].
Available from: http://dspace.library.uu.nl:8080/handle/1874/187075.
Council of Science Editors:
Bastiaansen KCJT. Wnt signaling in hematopoietic stem cell maintenance. [Masters Thesis]. Universiteit Utrecht; 2010. Available from: http://dspace.library.uu.nl:8080/handle/1874/187075
UCLA
23.
Chin, Chee Jia.
Forming the hematopoietic stem cell niche from pluripotent stem cells.
Degree: Cellular & Molecular Pathology, 2016, UCLA
URL: http://www.escholarship.org/uc/item/5090j0jj
► Hematopoietic stem cells (HSCs) are characterized by their ability to self-renew and contribute to multi-lineage differentiation, critical functions that ensure homeostatic production of all blood…
(more)
▼ Hematopoietic stem cells (HSCs) are characterized by their ability to self-renew and contribute to multi-lineage differentiation, critical functions that ensure homeostatic production of all blood cells throughout life. A major challenge in the field is the inability to culture HSCs without compromising self-renewal. My goal was to reconstruct an optimal hematopoietic niche from mesodermal differentiation of human pluripotent stem cells (hPSC) to facilitate the maintenance of functional HSCs. Initial characterization of the human fetal bone marrow and adult adipose tissues revealed that a subpopulation of CD146+ perivascular cells was capable of supporting the self-renewal of transplantable human cord blood HSCs ex vivo. Vector integration site-based lineage tracing technology was utilized to gain insights into the stages through which hPSC differentiate into mesodermal derivatives of the HSC niche. High throughput sequencing revealed the presence of mesodermal progenitors with trilineage (hematopoietic, endothelial and mesenchymal) potential during hPSC differentiation and uncovered the lineage bifurcation of hematopoietic and mesenchyme early on in separated bipotent populations. The hPSC-derived mesenchymal populations were further studied in relation to their ability to promote or inhibit HSC maintenance, leading to the discovery of a population that was phenotypically, functionally and molecularly similar to primary human perivascular cells of the HSC niche. These findings elucidated lineage commitment events during early human embryogenesis and informed strategies to optimize the therapeutic development of cell lineages from hPSC.
Subjects/Keywords: Developmental biology; Hematopoiesis; hematopoietic stem cell niche; pericyte; pluripotent stem cells
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APA (6th Edition):
Chin, C. J. (2016). Forming the hematopoietic stem cell niche from pluripotent stem cells. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/5090j0jj
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chin, Chee Jia. “Forming the hematopoietic stem cell niche from pluripotent stem cells.” 2016. Thesis, UCLA. Accessed February 16, 2020.
http://www.escholarship.org/uc/item/5090j0jj.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chin, Chee Jia. “Forming the hematopoietic stem cell niche from pluripotent stem cells.” 2016. Web. 16 Feb 2020.
Vancouver:
Chin CJ. Forming the hematopoietic stem cell niche from pluripotent stem cells. [Internet] [Thesis]. UCLA; 2016. [cited 2020 Feb 16].
Available from: http://www.escholarship.org/uc/item/5090j0jj.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chin CJ. Forming the hematopoietic stem cell niche from pluripotent stem cells. [Thesis]. UCLA; 2016. Available from: http://www.escholarship.org/uc/item/5090j0jj
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
24.
Koechlein, Claire.
Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration.
Degree: Biomedical Sciences, 2016, University of California – San Diego
URL: http://www.escholarship.org/uc/item/0cc0x1jq
► The hematopoietic system is maintained throughout the lifetime of an organism by hematopoietic stem cells (HSCs). HSCs are uniquely able to balance both self-renewal, to…
(more)
▼ The hematopoietic system is maintained throughout the lifetime of an organism by hematopoietic stem cells (HSCs). HSCs are uniquely able to balance both self-renewal, to maintain a population of stem cells, and differentiation, to produce all of the immune cells required for hematopoietic function. Further, in response to a severe injury, such as chemotherapy or radiation, HSCs are able to respond and regenerate the hematopoietic compartment. To better understand the intrinsic and extrinsic mechanisms that endow this functionality, I focused on two main facets of hematopoietic stem cell biology: the bone marrow microenvironment and metabolism. To compare the role of distinct bone marrow niches in hematopoiesis we developed two tools. First, a live calvarial bone marrow imaging system that allowed dynamic real-time tracking of individual cells. Secondly, a transgenic mouse that enabled the visualization of hematopoietic stem/progenitor cells (HSPCs) in vivo. To track HSPCs in real-time via live imaging, we developed a new Msi2-GFP knock-in reporter mouse. Using these tools, I determined that HSPCs display a preference for contacting the vasculature niche, as well as making long-term interactions there. Further application of these tools will continue to deepen the understanding of how HSPCs interact with and are influenced by their bone marrow microenvironment.To understand the role of metabolism in HSC function, I focused on uncovering the function of the monocarboxylate transporters 1 and 2 (MCT1/2). MCT1/2 were identified from a transcriptional analysis of genes impacted by the treatment of mice with G-CSF, which induces HSC proliferation and mobilization. Inhibition of MCT1/2 via AR-C155858 (AR-C) improved HSC function both in vitro and in vivo. AR-C improved bone marrow recovery after injury and the engraftment of mouse and human HSCs. This data supports the use of AR-C as a clinical tool to both aid hematopoietic regeneration and hematopoietic stem cell transplant efficacy. Collectively, this dissertation advances the understanding of mechanisms regulating homeostatic and regenerating HSCs. A thorough understanding of these mechanisms allows them to be manipulated for therapeutic uses to improve patient outcomes after hematopoietic injury and engraftment after transplantation.
Subjects/Keywords: Biology; Hematopoiesis; Hematopoietic Stem Cell; Regeneration; Stem Cells
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Koechlein, C. (2016). Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/0cc0x1jq
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Koechlein, Claire. “Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration.” 2016. Thesis, University of California – San Diego. Accessed February 16, 2020.
http://www.escholarship.org/uc/item/0cc0x1jq.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Koechlein, Claire. “Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration.” 2016. Web. 16 Feb 2020.
Vancouver:
Koechlein C. Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2020 Feb 16].
Available from: http://www.escholarship.org/uc/item/0cc0x1jq.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Koechlein C. Regulation of Hematopoietic Stem Cell Self-Renewal during Homeostasis and Regeneration. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/0cc0x1jq
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Texas Southwestern Medical Center
25.
Inra, Christopher N.
The Niche for Extramedullary Hematopoiesis in the Spleen.
Degree: 2017, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/6594
► The file named "INRA-DISSERTATION-2017.pdf" is the primary dissertation file. A supplemental movie file ("Video 1.mp4") is also available and may be viewed individually.
The ability…
(more)
▼ The file named "INRA-DISSERTATION-2017.pdf" is the primary dissertation file. A supplemental movie file ("Video 1.mp4") is also available and may be viewed individually.
The ability to regenerate niches or to create new niches after injury is critical to accelerate tissue repair and may underlie the regenerative capacity of mammalian tissues. Despite its physiological importance, almost nothing is known about how mammalian tissues activate facultative niches after injury. The mouse hematopoietic system provides a dynamic example of new stem cell niche activation. After hematopoietic injury, hematopoietic stem cells (HSCs) mobilize from the bone marrow to the spleen and participate in extramedullary hematopoiesis (EMH), which supplements bone marrow hematopoiesis for as long as the hematopoietic stress persists. The induction of hematopoiesis in the spleen involves the creation or activation of a facultative niche in the spleen, yet no niche in this tissue has been characterized. Understanding the nature of the extramedullary niche in the spleen will clarify how the hematopoietic microenvironment regulates HSC and other progenitor function to reestablish homeostasis after injury.
The work in this thesis identifies the cell types in the spleen that are physiologically important sources of the niche factors SCF and CXCL12 during extramedullary hematopoiesis. By using fluorescent reporter alleles for each niche factor, I have discovered that spleen endothelial and perivascular stromal cells secrete SCF, and a subset of spleen perivascular stromal cells secretes CXCL12. Conditional deletion of Scf from spleen endothelial or perivascular stromal cells impairs EMH after injury by depleting HSCs and myeloerythroid progenitors from the spleen. Conditional deletion of Cxcl12 from spleen perivascular stromal cells impairs EMH by depleting myeloerythroid progenitors and mobilizing a minority of HSCs from the spleen.
This work conclusively demonstrates that spleen endothelial cells maintain EMH by secreting SCF, and spleen perivascular stromal cells maintain EMH by secreting both SCF and CXCL12. These cell types represent the first stromal populations in the spleen shown to maintain HSCs and EMH after injury. Further analyses of these cells during injury may reveal how hematopoietic niches are created.
Advisors/Committee Members: Castrillon, Diego H., Morrison, Sean J., Buszczak, Michael, Cleaver, Ondine.
Subjects/Keywords: Hematopoiesis, Extramedullary; Hematopoietic Stem Cells; Spleen; Stem Cell Niche
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Inra, C. N. (2017). The Niche for Extramedullary Hematopoiesis in the Spleen. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/6594
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Inra, Christopher N. “The Niche for Extramedullary Hematopoiesis in the Spleen.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed February 16, 2020.
http://hdl.handle.net/2152.5/6594.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Inra, Christopher N. “The Niche for Extramedullary Hematopoiesis in the Spleen.” 2017. Web. 16 Feb 2020.
Vancouver:
Inra CN. The Niche for Extramedullary Hematopoiesis in the Spleen. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2152.5/6594.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Inra CN. The Niche for Extramedullary Hematopoiesis in the Spleen. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/6594
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Rochester
26.
Charles, Nichola.
A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins.
Degree: PhD, 2009, University of Rochester
URL: http://hdl.handle.net/1802/6743
► Hematopoietic stem cell transplantation (HSCT) is used to treat both malignant and non-malignant diseases and enrichment of the hematopoietic stem and progenitor cells (HSPCs) has…
(more)
▼ Hematopoietic stem cell transplantation (HSCT) is
used to treat both malignant and non-malignant diseases and
enrichment of the hematopoietic stem and progenitor cells (HSPCs)
has the potential to reduce the likelihood of graft vs. host
disease or relapse, potentially fatal complications associated with
the therapy. Current commercial HSPC isolation technologies rely
solely on the CD34 surface marker and while they have proven to be
invaluable, HSCT that utilize very pure samples of CD34+ HSPCs is
associated with higher incidences of failure and longer time for
engraftment. Since HSPCs must interact with selectins to
successfully home to the marrow, a functional technique to isolate
HSPCs based on their interaction with immobilized selectins might
improve HSCT by simultaneously purifying the HSPCs and selecting
only those cells with the highest probability of homing to the
marrow To assess the behavior of adult bone marrow (ABM)
cells on immobilized selectins, purified CD34+ and CD34- ABM cells
were perfused over immobilized P-, E- and L-selectin-IgG at
physiologic wall shear stresses. CD34+ ABM cells generally
exhibited lower rolling velocities and higher retention than CD34-
ABM cells on all three selectins. For the experimental conditions
used, it is theoretically possible to increase the purity of CD34+
ABM cells starting from 1 - 5% to between 5.2% - 36.1%.
Additionally, hybrid surfaces of immobilized antibody and selectin
were used to create differences in rolling velocities between CD34+
KG1a cells and CD34- HL60 cells, acute myeloid leukemia cell lines
with no inherent differences in rolling velocity on P-selectin-IgG
alone. The relationship between yield and purity is reciprocal, but
optimal cell enrichment should be achievable within 10 minutes,
much faster than most current commercially available systems.
Devices that might enrich CD34+ ABM cells by
capitalizing on the differential rolling velocity remain an
unfeasible option due to geometric and manufacturing constraints.
Laboratory-scale testing of the efficiency of P-selectin-mediated
CD34+ ABM cell enrichment exploited the differential cell retention
using a cylindrical flow chamber and various wall shear stresses
and perfusion times. Short perfusion times and low wall shear
stresses consistently resulted in the highest CD34+ ABM cell yield,
and the enrichment procedure could be completed in a short time (≤
15 minutes), however a threshold for the enrichment was observed,
generally ~ 3-fold. Although CD34+ ABM cells enriched using
Dynabeads immunomagnetic cell enrichment technique had higher
purities and fold enrichment, the yield was lower than
P-selectin-mediated enrichment depending on the flow conditions
used. Gravitational sedimentation was used to recruit
cells to the surface to ensure maximum cell accumulation and
interaction, but this reduced the efficiency of the device by at
least 50% since only the lower surfaces were used. Experimental
study and computational fluid dynamics (CFD) was used to
investigate how three tubing…
Subjects/Keywords: CD34+ cells; P-selectin; Hematopoietic stem cells; E-selectin; L-selectin
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Charles, N. (2009). A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/6743
Chicago Manual of Style (16th Edition):
Charles, Nichola. “A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins.” 2009. Doctoral Dissertation, University of Rochester. Accessed February 16, 2020.
http://hdl.handle.net/1802/6743.
MLA Handbook (7th Edition):
Charles, Nichola. “A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins.” 2009. Web. 16 Feb 2020.
Vancouver:
Charles N. A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins. [Internet] [Doctoral dissertation]. University of Rochester; 2009. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/1802/6743.
Council of Science Editors:
Charles N. A Novel Method for Enriching CD34+ Hematopoietic Cells
from Adult Bone Marrow Using Immobilized Selectins. [Doctoral Dissertation]. University of Rochester; 2009. Available from: http://hdl.handle.net/1802/6743
University of Lund
27.
Kristiansen, Trine.
Switching ON Fetal B Lymphopoiesis.
Degree: 2018, University of Lund
URL: https://lup.lub.lu.se/record/39628366-ea68-464d-b9d1-a05076883779
;
https://portal.research.lu.se/ws/files/42490856/TAK_Kappa.pdf
► B-1a cells are innate-like lymphocytes that develop primarily during fetal and neonatal life, whereas adult bone marrow (BM) hematopoietic stem cells (HSCs) preferentially give rise…
(more)
▼ B-1a cells are innate-like lymphocytes that develop
primarily during fetal and neonatal life, whereas adult bone marrow
(BM) hematopoietic stem cells (HSCs) preferentially give rise to
follicular B-2 cells. Functioning at the interface of the innate
and adaptive immune systems, B-1a cells provide a non-redundant
first line of defense prior to the temporally delayed establishment
of a B-2 cell response. The underlying causes for the developmental
attenuation in B-1a potential remain poorly resolved. HSCs undergo
a functional switch in neonatal mice hallmarked by a decrease in
self-renewing divisions and entry into quiescence. The timing of
this switch around 3 weeks of age correlates with the change in B
cell output from B-1a potent to predominantly B-2 restricted. We
hypothesized that the cellular basis for this developmental
attenuation in B-1a cell output is a consequence of a shift in stem
cell state during ontogeny. Using cellular barcoding for in vivo
single-cell resolution analyses, we found that fetal liver
definitive HSCs gave rise to both B-1a and B-2 cells. To directly
assess whether a developmental shift in HSC state can lead to a
selective loss in B-1a potential on a per cell basis, we performed
longitudinal comparison of repopulation potential by following
barcoded founder cells across serial transplantations. Whereas B-1a
potential diminished over time, B-2 output was maintained. B-1a
potential could be reinitiated in a subset of adult HSCs by ectopic
expression of the RNA binding protein LIN28B, a key regulator of
fetal hematopoiesis. This coincided with the clonal reversal to a
fetal-like elevated self-renewal and repopulation potential. These
results anchor the attenuation of B-1a cell output to fetal HSC
behavior and demonstrate that the developmental decline in
regenerative potential represents a reversible HSC state. While
these data made clear that developmentally restricted hematopoietic
origins cannot fully account for the postnatal decline in B-1a
output, the underlying mechanism for the positive selection and
output of B-1a cells remains elusive. Recent studies showed that
ectopic expression of Lin28b in adult pro-B cells was sufficient to
potentiate fetal-like B-1a cell output. This led us to next
hypothesize that Lin28b may play an important role during the
latter part of B lymphopoiesis to potentiate the positive selection
of B-1a cells early in life. We showed that CD5 levels of B-1 cells
are developmentally set in the immature B cell stage and correlates
with self-reactivity. Genetic perturbation studies show that Lin28b
is necessary and sufficient for efficient positive selection of
B-1a cells and potentiates neonatal immature B cell CD5 expression
in a dose dependent fashion. Importantly, our results uncouple
positive selection from specific B cell receptor identities,
implicating the heterochronic RNA-binding protein LIN28b as the
missing link that regulates the developmental attenuation in B-1a
cell output through relaxing the permissiveness of B cell
selection. Our findings shed…
Subjects/Keywords: B-1 B cells; Lin28; Fetal hematopoietic stem cells
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APA (6th Edition):
Kristiansen, T. (2018). Switching ON Fetal B Lymphopoiesis. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/39628366-ea68-464d-b9d1-a05076883779 ; https://portal.research.lu.se/ws/files/42490856/TAK_Kappa.pdf
Chicago Manual of Style (16th Edition):
Kristiansen, Trine. “Switching ON Fetal B Lymphopoiesis.” 2018. Doctoral Dissertation, University of Lund. Accessed February 16, 2020.
https://lup.lub.lu.se/record/39628366-ea68-464d-b9d1-a05076883779 ; https://portal.research.lu.se/ws/files/42490856/TAK_Kappa.pdf.
MLA Handbook (7th Edition):
Kristiansen, Trine. “Switching ON Fetal B Lymphopoiesis.” 2018. Web. 16 Feb 2020.
Vancouver:
Kristiansen T. Switching ON Fetal B Lymphopoiesis. [Internet] [Doctoral dissertation]. University of Lund; 2018. [cited 2020 Feb 16].
Available from: https://lup.lub.lu.se/record/39628366-ea68-464d-b9d1-a05076883779 ; https://portal.research.lu.se/ws/files/42490856/TAK_Kappa.pdf.
Council of Science Editors:
Kristiansen T. Switching ON Fetal B Lymphopoiesis. [Doctoral Dissertation]. University of Lund; 2018. Available from: https://lup.lub.lu.se/record/39628366-ea68-464d-b9d1-a05076883779 ; https://portal.research.lu.se/ws/files/42490856/TAK_Kappa.pdf
University of British Columbia
28.
Szilvassy, Stephen Joseph.
Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
.
Degree: 1990, University of British Columbia
URL: http://hdl.handle.net/2429/31003
► The hemopoietic system Is organized as a hierarchy of hemopoietic cell populations distinguished by differences in their proliferation and differentiation potential. Studies using short-term in…
(more)
▼ The hemopoietic system Is organized as a hierarchy of hemopoietic cell populations distinguished by differences in their proliferation and differentiation potential. Studies using short-term in vitro and in vivo assays based on colony formation in semi-solid medium, or in the spleens of lethally irradiated mice, respectively, have shown that these procedures detect primarily lineage-restricted progenitor types and have provided much information about the characteristics and regulation of such cells. Assessment of lymphoid and myeloid tissue reconstitution after more prolonged periods following transplantation has established the existence of a more primitive stem cell type; however, the retrospective nature of these complex analyses has Impeded characterization and purification of these cells. My first objective was to develop a procedure for the selective isolation of stem cells with short-term in vitro and in vivo multilineage differentiation potential. For this I devised a single-step, four-parameter fluorescence activated cell sorting procedure In which cells were selected according to their forward and orthogonal light-scattering properties, and their surface expression of the Thy-1 and H-2K antigens. Application of this procedure to marrow cells from mice treated 4 days previously with 150 mg/kg of 5-fluorouracil showed that it could be used to sort a subpopulation that was enriched 100-fold in CFU-GEMM and in which 1 in 4 cells was a day 12 CFU-S.
To determine the extent to which stem cells with long-term lympho-myeloid repopulating potential had been copurified, I undertook to develop a quantitative procedure that might allow this primitive cell population to be measured and hence characterized on a routine basis. This required an assay that would detect donor-derived hemopoiesis exclusively, and that was sensitive enough for the detection of limiting numbers of cells with long-term lympho-myeloid repopulating potential. This was shown to be possible using a competitive repopulation assay in which lethally irradiated female recipients were transplanted with male "test" cells together with a second suspension of female cells with adequate short-term repopulating activity but greatly diminished long-term repopulating potential. These sex differences were then used to specifically identify the 5 week progeny of stem cells in the test suspension. Assessment of the sorted day 4 5-FU marrow population revealed that it was capable of repopulating all hemopoietic organs after transplantation and that an enrichment of 30-fold over unseparated, 5-FU-treated marrow had been achieved.
My second objective was to determine whether the competitive long-term lymphoid and myeloid repopulation obtained with these sorted cells was due to the activity of Individual stem cells with a dual potential for lymphopoiesis and myelopoiesis. For this I used retroviral-infection to uniquely mark sorted cells In vitro, and then transplanted them in sufficiently low numbers to allow individual regenerated clones to be detected and…
Subjects/Keywords: Hematopoietic stem cells;
Hematopoietic Stem Cells – isolation & purification
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Manager
APA (6th Edition):
Szilvassy, S. J. (1990). Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
. (Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/31003
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Szilvassy, Stephen Joseph. “Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
.” 1990. Thesis, University of British Columbia. Accessed February 16, 2020.
http://hdl.handle.net/2429/31003.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Szilvassy, Stephen Joseph. “Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
.” 1990. Web. 16 Feb 2020.
Vancouver:
Szilvassy SJ. Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
. [Internet] [Thesis]. University of British Columbia; 1990. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2429/31003.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Szilvassy SJ. Purification and characterization of murine long-term lympho-myeloid repopulating hemopoietic stem cells
. [Thesis]. University of British Columbia; 1990. Available from: http://hdl.handle.net/2429/31003
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Deakin University
29.
Gregorio-King, Claudia C.
Identification of novel genes differentially expressed in haemopoietic progenitor cells.
Degree: School of Health Sciences, 2001, Deakin University
URL: http://hdl.handle.net/10536/DRO/DU:30023116
► The biochemical and molecular processes that maintain the stem cell pool, and govern the proliferation and differentiation of haemopoietic stem/progenitor cells (HSPCs) have been widely…
(more)
▼ The biochemical and molecular processes that maintain the stem cell pool, and govern the proliferation and differentiation of haemopoietic stem/progenitor cells (HSPCs) have been widely investigated but are incompletely understood. The purpose of this study was to identify and characterise novel genes that may play a part in regulating the mechanisms that control the proliferation, differentiation and self-renewal of human HSPCs. Reverse transcription differential display polymerase chain reaction (dd-PCR) was used to identify differences in gene expression between a HSPC population defined by expression of the CD34 phenotype, and the more mature CD34 depleted populations. A total of 6 differentially expressed complementary deoxyribonucleic acid (cDNA) sequences were identified. Four of these transcripts were homologous to well characterised genes, while two (band 1 and band 20) were homologous to unknown and uncharacterised partial gene sequences on the GenBank database and were thus chosen for further investigation. The partial cDNA sequences for band 1 and band 20 were designated ORP-3 and MERP-1 (respectively) due to homologies with other well-characterised gene families. Differential expression of the ORP-3 and MERP-1 genes was confirmed using Taqman™ real-time polymerase chain reaction (PCR) with 3 - 4-fold and 4-10 -fold higher levels in the CD34+ fractions of haemopoietic cells compared to CD34- populations respectively. Additionally, expression of both these genes was down regulated with proliferation and differentiation of CD34+ cells further confirming higher expression in a less differentiated subset of haemopoietic cells. The full coding sequences of ORP-3 and MERP-1 were elucidated using bioinformatics, rapid amplification of cDNA ends (RACE) and PCR amplification. The MERP-1 cDNA is 2600 nucleotides (nt) long, and localizes by bioinformatics to chromosome 7.. It consists of three exons and 2 introns spanning an entire length of 31.4 kilobases (kb). The MERP-1 open reading frame (ORF) codes for a putative 344 amino acid (aa) type II transmembrane protein with an extracellular C-terminal ependymin like-domain and an intracellular N-terminal sequence with significant homology to the cytoplasmic domains of members of the protocadherin family of transmembrane glycoproteins. Ependymins and protocadherins are well-characterised calcium-dependant cell adhesion glycoproteins. Although the function of MERP-1 remains to be elucidated, it is possible that MERP-1 like its homologues plays a role in calcium dependent cell adhesion. Differential expression of the MERP-1 gene in haemopoietic cells suggests a role in haemopoietic stem cell proliferation and differentiation, however, its broad tissue distribution implies that it may also play a role in many cell types. Characterization of the MERP-1 protein is required to elucidate these possible roles. The ORP-3 cDNA is 6631nt long, and localizes by bioinformatics to chromosome 7pl5-p21. It consists of 23 exons and 22 introns spanning an entire length of 183.5kb. The…
Subjects/Keywords: Hematopoietic stem cells; Hematopoietic stem cells - Growth; Genes
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APA (6th Edition):
Gregorio-King, C. C. (2001). Identification of novel genes differentially expressed in haemopoietic progenitor cells. (Thesis). Deakin University. Retrieved from http://hdl.handle.net/10536/DRO/DU:30023116
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gregorio-King, Claudia C. “Identification of novel genes differentially expressed in haemopoietic progenitor cells.” 2001. Thesis, Deakin University. Accessed February 16, 2020.
http://hdl.handle.net/10536/DRO/DU:30023116.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gregorio-King, Claudia C. “Identification of novel genes differentially expressed in haemopoietic progenitor cells.” 2001. Web. 16 Feb 2020.
Vancouver:
Gregorio-King CC. Identification of novel genes differentially expressed in haemopoietic progenitor cells. [Internet] [Thesis]. Deakin University; 2001. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/10536/DRO/DU:30023116.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gregorio-King CC. Identification of novel genes differentially expressed in haemopoietic progenitor cells. [Thesis]. Deakin University; 2001. Available from: http://hdl.handle.net/10536/DRO/DU:30023116
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston University
30.
Thomas, Dolly.
The role of IGF2 in the regulation of hematopoietic stem cell function.
Degree: PhD, Cell & Molecular Biology, 2014, Boston University
URL: http://hdl.handle.net/2144/15084
► Maintenance of the hematopoietic system is dependent upon the proper regulation and orchestrated functions of the hematopoietic stem cell (HSC) pool. A number of extrinsic…
(more)
▼ Maintenance of the hematopoietic system is dependent upon the proper regulation and orchestrated functions of the hematopoietic stem cell (HSC) pool. A number of extrinsic signaling pathways and intrinsic regulators have been found to regulate HSC processes. However a full understanding of the ability of HSC to balance the processes of self-renewal, quiescence, and lineage specification is not yet clear. We therefore set out to identify novel HSC regulators by comparative gene expression analysis of whole genome transcriptomes generated for long-term (LT)-HSC (Hoechst low/- Lin- Sca1+ cKit+ CD34-), short-term (ST)-HSC (Hoechst low/- Lin- Sca1+ cKit+ CD34+), and non-HSC (Hoechst+) of the bone marrow. These studies identified IGF2 as one of the most differentially expressed genes within LT-HSC, suggesting a potential role for IGF2 in the regulation of HSC.
Using a combination of lentiviral-mediated overexpression and knockdown experiments, we found IGF2 to confer enhanced self-renewal in vitro and in vivo. Overexpression of IGF2 resulted in an increased percentage of multi-lineage colonies within colony-forming unit (CFU) assays without affecting lineage specification. In vivo, serial bone marrow transplantation revealed that IGF2 within HSC enhances short-term and long-term donor contribution.
Analysis of the expression of key cell cycle regulators revealed that IGF2 induced upregulation of p57 expression specifically within HSC. This upregulation could be attributed to differences in the methylation status of the p57 promoter in HSC compared to other progenitor and mature blood cell populations. p57, a member of the Cip/Kip family of cyclin dependent kinase inhibitors, has recently been shown to be required for the regulation of HSC quiescence and long-term self-renewal. Analysis of bone marrow obtained from primary and secondary transplant recipients showed that overexpression of IGF2 resulted in an increased percentage of quiescent HSC. Treatment of HSC overexpressing IGF2 with LY294002, a PI3K-Akt inhibitor, prevented IGF2-mediated upregulation of p57 expression. These findings demonstrate that within HSC, IGF2 induces p57 expression through activation of the PI3K-Akt pathway to regulate HSC quiescence. We have identified a novel role for IGF2 in HSC function, providing new insights into the biology of HSC and opening potential platforms for the development of better therapies involving HSC-mediated hematopoietic reconstitution.
Subjects/Keywords: Medicine; Hematopoiesis; Hematopoietic stem cells; Insulin-like growth factor 2; p57; Self-renewal; Stem cells
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Thomas, D. (2014). The role of IGF2 in the regulation of hematopoietic stem cell function. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/15084
Chicago Manual of Style (16th Edition):
Thomas, Dolly. “The role of IGF2 in the regulation of hematopoietic stem cell function.” 2014. Doctoral Dissertation, Boston University. Accessed February 16, 2020.
http://hdl.handle.net/2144/15084.
MLA Handbook (7th Edition):
Thomas, Dolly. “The role of IGF2 in the regulation of hematopoietic stem cell function.” 2014. Web. 16 Feb 2020.
Vancouver:
Thomas D. The role of IGF2 in the regulation of hematopoietic stem cell function. [Internet] [Doctoral dissertation]. Boston University; 2014. [cited 2020 Feb 16].
Available from: http://hdl.handle.net/2144/15084.
Council of Science Editors:
Thomas D. The role of IGF2 in the regulation of hematopoietic stem cell function. [Doctoral Dissertation]. Boston University; 2014. Available from: http://hdl.handle.net/2144/15084
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