Fluid Shear Stress Promotes Mouse Embryonic Stem Cell Pluripotency via E-cadherin Mechanotransduction

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atmire.migration.oldid5732
dc.contributor.advisorRancourt, Derrick
dc.contributor.authorDay, Bradley
dc.contributor.committeememberKallos, Michael
dc.contributor.committeememberMacNaughton, Wallace
dc.contributor.committeememberMains, Paul
dc.date.accessioned2017-07-04T20:45:14Z
dc.date.available2017-07-04T20:45:14Z
dc.date.issued2017
dc.date.submitted2017en
dc.description.abstractEmbryonic stem cells (ESCs) are capable of self-renewal and differentiation into any cell type; this is a powerful tool in generating different cell lineages for regenerative medicine. Stirred suspension bioreactors have been developed as a way to culture ESCs quickly and with minimal labour. Cells are stirred at 100 RPM, which has a maximum tip shear stress of 6 dyne/cm2. We have discovered that cells grown under these conditions maintain pluripotency even in the absence of leukemia inhibitory factor (LIF), an obligate pluripotency maintenance factor. Prior studies have shown that cells can sense physical signals such as shear stress in their environment and modulate a biochemical response through mechanotransduction. In this thesis, I show a link between mechanotransduction and the maintenance of pluripotency. In response to shear stress, β-catenin, a member of the wnt pathway is translocated to the nucleus. Inhibition of β-catenin in the bioreactor results in a decrease in pluripotency gene expression. The disruption of vinculin, a protein recruited to the periphery of the cell in response to shear stress, also leads to a reduction in bioreactor induced pluripotency. Direct manipulation of cells bound to Ecadherin peptides with shear stress generates nuclear β-catenin translocation as well as accumulation of vinculin on the periphery of the cell. These results indicate that shear stress induces bioreactor maintained pluripotency, a phenomenon we have named mechanopluripotency.en_US
dc.identifier.citationDay, B. (2017). Fluid Shear Stress Promotes Mouse Embryonic Stem Cell Pluripotency via E-cadherin Mechanotransduction (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26198en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/26198
dc.identifier.urihttp://hdl.handle.net/11023/3916
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBiology--Cell
dc.subjectBiology--Molecular
dc.subject.otherpluripotency
dc.subject.othermechanotransduction
dc.subject.otherstem cell
dc.subject.othershear stress
dc.titleFluid Shear Stress Promotes Mouse Embryonic Stem Cell Pluripotency via E-cadherin Mechanotransduction
dc.typedoctoral thesis
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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