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dc.contributor.advisorLi, Mo
dc.contributor.authorAlsolami, Samhan M.
dc.date.accessioned2019-12-03T10:40:30Z
dc.date.available2019-12-03T10:40:30Z
dc.date.issued2019-10
dc.identifier.doi10.25781/KAUST-PGQD1
dc.identifier.urihttp://hdl.handle.net/10754/660389
dc.description.abstractThe discovery of human pluripotent stem cells (hPSCs) has opened a new field called regenerative medicine that offers new strategies for curing diseases and drug discovery. It also provides the means of regenerating disease-relevant cells in vitro for disease modeling, and the possibility of cell replacement therapy. Among the most promising applications of hPSCs technology is the generation of blood cells that can be used for engraftment or transfusion in the clinic. Generating engraftable hematopoietic stem cells from hPSCs in vitro can fulfill the promise of using hPSCs to cure human diseases. Making functional HSCs in vitro from hPSCs remains an elusive goal. There are key pathways that are misregulated during hPSCs differentiation, which could impair the engraftment potential of hPSCs. WNT signaling is needed in the early phase of differentiation. However, evidence from mouse models and human development show that WNT signaling is downregulated during the maturation of HSCs. Therefore, we hypothesize that mimicking the dynamics of WNT signaling temporally during the differentiation could improve the functional maturation of differentiated HPCs. To this end, we have established an inducible gene activation system based on dCas9-VPR that can activate endogenous loci. We performed targeted activation of negative regulators of WNT. The system has shown promise in specific activation of WNT negative regulators, AXIN2 and APC2, but it needs further optimization to be able to steer cell fate and obtain functional HSCs.
dc.language.isoen
dc.subjectdCas9
dc.subjectPluripotent Stem Cells
dc.titleThe Role of WNT-beta-Catenin Pathway in the Specification of Primitive and Definitive Hematopoiesis during Differentiation of Pluripotent Stem Cells
dc.typeThesis
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.rights.embargodate2020-12-03
thesis.degree.grantorKing Abdullah University of Science and Technology
dc.contributor.committeememberAdamo, Antonio
dc.contributor.committeememberBlilou, Ikram
thesis.degree.disciplineBioscience
thesis.degree.nameMaster of Science
dc.rights.accessrightsAt the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis will become available to the public after the expiration of the embargo on 2020-12-03.
refterms.dateFOA2020-12-03T00:00:00Z
kaust.request.doiyes


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