{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"O-linked N-acetylglucosamine in differentiation and gene expression of mouse and human pluripotent stem cells","abstract":"Peptide posttranslational modifications have been shown to regulate multiple aspects of cell signalling, thereby influencing cellular functions. The addition of O-linked Nacetylglucosamine to serine or threonine residues (O-GlcNAcylation) of proteins has only recently been characterized and its overall role in cell signalling remains elusive to date. Recent studies suggest an essential role of O-GlcNAcylation on the viability and pluripotency of mouse and human embryonic stem (ES) cells. Here we show that increased levels of O-GlcNAcylation in response to specific inhibition of O-GlcNAc hydrolase (Oga) hinder mouse ES cell differentiation. In addition to these findings, I could also demonstrate that increased O-GlcNAcylation leads to expression of a gene set normally epigenetically repressed in mouse ES cells and associated with a subpopulation resembling cells in the 2-cell-stage embryo. I also extended our lab's investigations to human induced pluripotent stem (iPS) cells. While mesendodermal differentiation remains unaffected by high O-GlcNAc levels, neural differentiation is severely disrupted in these cells. Human iPS cells with elevated O-GlcNAcylation are unable to commit to the ectodermal lineage and fail to organize in neural tube-like structures, so-called neural rosettes. Following these observations we performed mRNA sequencing analysis on human iPS cells with high O-GlcNAc levels and found gene expression to be significantly altered. Genes affected by increased O-GlcNAcylation include modulators of key neural developmental processes, for example components of the bone morphogenic protein signalling cascade.","abstract_html":"Peptide posttranslational modifications have been shown to regulate multiple aspects of cell signalling, thereby influencing cellular functions. The addition of O-linked Nacetylglucosamine to serine or threonine residues (O-GlcNAcylation) of proteins has only recently been characterized and its overall role in cell signalling remains elusive to date. Recent studies suggest an essential role of O-GlcNAcylation on the viability and pluripotency of mouse and human embryonic stem (ES) cells. Here we show that increased levels of O-GlcNAcylation in response to specific inhibition of O-GlcNAc hydrolase (Oga) hinder mouse ES cell differentiation. In addition to these findings, I could also demonstrate that increased O-GlcNAcylation leads to expression of a gene set normally epigenetically repressed in mouse ES cells and associated with a subpopulation resembling cells in the 2-cell-stage embryo. I also extended our lab's investigations to human induced pluripotent stem (iPS) cells. While mesendodermal differentiation remains unaffected by high O-GlcNAc levels, neural differentiation is severely disrupted in these cells. Human iPS cells with elevated O-GlcNAcylation are unable to commit to the ectodermal lineage and fail to organize in neural tube-like structures, so-called neural rosettes. Following these observations we performed mRNA sequencing analysis on human iPS cells with high O-GlcNAc levels and found gene expression to be significantly altered. Genes affected by increased O-GlcNAcylation include modulators of key neural developmental processes, for example components of the bone morphogenic protein signalling cascade.","abstract_has_math":false,"creators":["Domke, Tanja Carolina Elisabeth"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Stavridis, Marios"],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-24T02:08:19Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Stavridis, Marios"]},{"key":"dc:creator","label":"Author","values":["Domke, Tanja Carolina Elisabeth"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Life and Biomedical Sciences Education"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights.embargodate","label":"Dc Rights Embargodate","values":["2017-11-16"]},{"key":"dc:rights.embargoreason","label":"Dc Rights Embargoreason","values":["/dk/atira/pure/core/document/studentthesisembargoreason/commercialexploitation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69","https://discovery.dundee.ac.uk/en/studentTheses/e84ff9a1-a4ab-41d0-828c-60a191b42c69"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/10869029/thesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Peptide posttranslational modifications have been shown to regulate multiple aspects of cell signalling, thereby influencing cellular functions. The addition of O-linked Nacetylglucosamine to serine or threonine residues (O-GlcNAcylation) of proteins has only recently been characterized and its overall role in cell signalling remains elusive to date. Recent studies suggest an essential role of O-GlcNAcylation on the viability and pluripotency of mouse and human embryonic stem (ES) cells. Here we show that increased levels of O-GlcNAcylation in response to specific inhibition of O-GlcNAc hydrolase (Oga) hinder mouse ES cell differentiation. In addition to these findings, I could also demonstrate that increased O-GlcNAcylation leads to expression of a gene set normally epigenetically repressed in mouse ES cells and associated with a subpopulation resembling cells in the 2-cell-stage embryo. I also extended our lab's investigations to human induced pluripotent stem (iPS) cells. While mesendodermal differentiation remains unaffected by high O-GlcNAc levels, neural differentiation is severely disrupted in these cells. Human iPS cells with elevated O-GlcNAcylation are unable to commit to the ectodermal lineage and fail to organize in neural tube-like structures, so-called neural rosettes. Following these observations we performed mRNA sequencing analysis on human iPS cells with high O-GlcNAc levels and found gene expression to be significantly altered. Genes affected by increased O-GlcNAcylation include modulators of key neural developmental processes, for example components of the bone morphogenic protein signalling cascade."]},{"key":"dc:title","label":"Title","values":["O-linked N-acetylglucosamine in differentiation and gene expression of mouse and human pluripotent stem cells"]}]}],"canonical_facts":{"dc:contributor.advisor":["Stavridis, Marios"],"dc:creator":["Domke, Tanja Carolina Elisabeth"],"dc:date":["2016"],"dc:date.issued":["2016"],"dc:description.abstract":["Peptide posttranslational modifications have been shown to regulate multiple aspects of cell signalling, thereby influencing cellular functions. The addition of O-linked Nacetylglucosamine to serine or threonine residues (O-GlcNAcylation) of proteins has only recently been characterized and its overall role in cell signalling remains elusive to date. Recent studies suggest an essential role of O-GlcNAcylation on the viability and pluripotency of mouse and human embryonic stem (ES) cells. Here we show that increased levels of O-GlcNAcylation in response to specific inhibition of O-GlcNAc hydrolase (Oga) hinder mouse ES cell differentiation. In addition to these findings, I could also demonstrate that increased O-GlcNAcylation leads to expression of a gene set normally epigenetically repressed in mouse ES cells and associated with a subpopulation resembling cells in the 2-cell-stage embryo. I also extended our lab's investigations to human induced pluripotent stem (iPS) cells. While mesendodermal differentiation remains unaffected by high O-GlcNAc levels, neural differentiation is severely disrupted in these cells. Human iPS cells with elevated O-GlcNAcylation are unable to commit to the ectodermal lineage and fail to organize in neural tube-like structures, so-called neural rosettes. 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