The effect of survivin expression on pluripotency factors in human embryonic stem cells

dc.contributor.advisorNavara, Christopher S.
dc.contributor.advisorMcCarrey, John
dc.contributor.authorMull, Amber N.
dc.contributor.committeeMemberHermann, Brian P.
dc.contributor.committeeMemberLeBaron, Richard
dc.contributor.committeeMemberYew, Patricia R.
dc.date.accessioned2024-02-12T18:30:01Z
dc.date.available2024-02-12T18:30:01Z
dc.date.issued2014
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractThe BIRC5 gene encodes the oncofetal protein SURVIVIN, as well as four additional splice variants (Ex3, 2B, 3B and 2a). SURVIVIN, an inhibitor of apoptosis, is also a chromosomal passenger protein (CPP). Previous results have demonstrated that SURVIVIN is expressed at high levels in embryonic stem cells, and its expression has been linked to pluripotency. However, these studies did not address the role of or the expression of the other four splice variants. The central hypothesis of this dissertation was that SURVIVIN and/or its' variants are required for maintaining pluripotency. The objective of this dissertation was to determine the extent to which SURVIVIN contributes to the regulation of pluripotency in human embryonic stem cells by regulating the expression of key pluripotency factors and through regulation of the cell cycle. We demonstrate that all SURVIVIN variants are expressed at significantly higher levels in human embryonic stem (hES) cells than in differentiated cells. We then describe the subcellular localization of the three most highly expressed variants and found that while SURVIVIN displayed canonical CPP localization in mitotic cells, SURVIVIN-Ex3 and SURVIVIN-2B did not localize as a CPP. The alternative splice variants have little to no expression in somatic tissues however we identified high expression levels in human ES cells indicating that the variants may have a function in pluripotent cells that they could not have in somatic cells due to their lack of expression. We used inducible shRNA against SURVIVIN and its' splice variants to inhibit expression in a titratable fashion and observed a subsequent decrease in pluripotency factors OCT4 and NANOG mRNA, and SOX2 and LIN28A protein suggesting a role for SURVIVIN in maintenance of pluripotency. Utilizing immunoprecipitation techniques, we identified a previously unknown interaction between SURVIVIN and LIN28A in human ES cells. The pluripotent cell cycle plays a vital role in the regulation of pluripotency so we conducted a comprehensive review of current literature. SURVIVIN has been implicated in the control of G 1 phase of cancer cells leading us to hypothesize that SURVIVIN may function to regulate pluripotency via a cell cycle regulatory mechanism. However, in the experiments performed in this dissertation, we did not identify an increase in the length of G 1 after SURVIVIN inhibition in our human embryonic stem cell system. This indicates SURVIVIN's regulation of pluripotency may exist independent of the G1 phase in pluripotent stem cells. Taken together, the research in this dissertation gives us insight into the complex role of SURVIVIN in pluripotent stem cells.
dc.description.departmentIntegrative Biology
dc.format.extent112 pages
dc.format.mimetypeapplication/pdf
dc.identifier.isbn9781321474664
dc.identifier.urihttps://hdl.handle.net/20.500.12588/4807
dc.languageen
dc.subjectEmbryonic stem cells
dc.subjectPluripotent factors
dc.subjectSURVIVIN
dc.subject.classificationCellular biology
dc.subject.classificationMolecular biology
dc.titleThe effect of survivin expression on pluripotency factors in human embryonic stem cells
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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