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dc.contributor.advisorGürsel, İhsan
dc.contributor.authorKeleş, Umur
dc.date.accessioned2016-01-08T20:18:38Z
dc.date.available2016-01-08T20:18:38Z
dc.date.issued2015
dc.identifier.urihttp://hdl.handle.net/11693/18368
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Graduate School of Engineering and Science of Bilkent University, 2015.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 2015.en_US
dc.descriptionIncludes bibliographical references leaves 53-63.en_US
dc.description.abstractGenetic and acquired liver diseases are generally progressive and life threatening with limited curative therapy options. Although organ transplantation is the most potent treatment, number of patients waiting for organ transplant far outnumbers the potential suitable donors. Recently, new alternative methods have been developed to generate functional hepatocytes which can directly be administered to patients. Generating hepatocytes from di erent cells derived from patient has been one of the most promising alternative. Direct conversion of terminally di erentiated cells into hepatocyte like cells has been reported previously. However, hepatocyte di erentiation from SV40 Large-T antigen expressing immortalized Mouse Embryonic Fibroblasts has not been reported. To this end, rst we have evaluated the e ects of individual and combined retroviral expression of liver lineage determining transcription factors: Hnf4 , Foxa2 and Foxa3. Single factor transduced immortal MEFs gave little or no signi cant epithelial marker expression. These conditions were also insu cient to induce liver speci c phenotype. However, combined expression of either Hnf4 +Foxa2 or Hnf4 +Foxa3 have resulted in an increased epithelial and liver speci c characteristics such as albumin expression and glycogen storage. To elucidate epigenetic background of this process we genotyped transgenic mouse strains with conditional knockout alleles of histone variants. Histone variant H3.3A conditional knockout immortal MEFs were also infected with Cre expressing retroviral vectors. Our studies indicated that, Large-T antigen immortalized MEFs can be transdifferentiated by using the protocol designated for primary MEFs. Additionally, by isolating and immortalizing genetically determined MEFs, we have established cell lines ready for understanding the roles of histone variants on trans differentiation. That will be the foundation of subsequent studies delineating e effects of histone variants on hepatocyte differentiation from MEFs.en_US
dc.description.statementofresponsibilityKeleş, Umuren_US
dc.format.extentxvi, 68 leaves, graphics, tablesen_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectInduced hepatocyteen_US
dc.subjectSV40en_US
dc.subjectImmortal MEFen_US
dc.subjectHnf4en_US
dc.subjectFoxa2en_US
dc.subjectFoxa3en_US
dc.subjectDirect conversionen_US
dc.subjectDirect conversionen_US
dc.subjectH3.3Aen_US
dc.subject.lccWI700 .K45 2015en_US
dc.subject.lcshHepotocytes--Transplantation--Laboratory manuals.en_US
dc.subject.lcshLiver cells--Laboratory manuals.en_US
dc.subject.lcshLiver cells--Transplantation.en_US
dc.titleDifferentiation of hepatocyte like cells from immortalized mouse embryonic fibroblasts harboring large T antigenen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreeM.S.en_US
dc.identifier.itemidB149513
dc.embargo.release2017-01-28


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