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AuthorSimon, Jana Katrindc.contributor.author
Date of accession2020-09-21T11:39:29Zdc.date.accessioned
Available in OPARU since2020-09-21T11:39:29Zdc.date.available
Year of creation2018dc.date.created
Date of first publication2020-09-21dc.date.issued
AbstractThe Protein Kinase D (PKD) family is set up by three highly conserved members, the isoenzymes PKD1, 2 and 3. PKDs are diacylglyerol-stimulated serine/ threonine protein kinases and form a subgroup of the Calcium/ Calmodulin Protein Kinase (CAMK) superfamily. Various stimuli lead to a Protein Kinase C (PKC)- dependent PKD-activation and the performance of multiple functions in diverse biological systems. A major role in physiological as well as tumour angiogenesis is attributed to PKD2. Angiogenesis is referred to as formation of new blood vessels from pre-existing vascular structures by endothelial cell differentiation. In contrast, vasculogenesis describes de novo blood vessel formation by endothelial cell differentiation from mesoderm during development. PKCs, the prominent upstream activators of PKDs, are known to drive lineage commitment in mouse embryonic stem cells (mESCs). Moreover, in the developing embryo, vasculogenesis and angiogenesis are closely linked. However, the role of PKDs during early embryonic cell fate decision and especially vasculogenesis largely remains elusive. To address this question, this study uses a combined gain- and loss-of-function approach in mouse embryonic stem cells for in vitro experiments, complemented with chicken chorioallantoic membrane (CAM) xenografts for an in vivo approach. This study demonstrates PKD2 to be strongly expressed in mESCs, followed by PKD3 and PKD1 only presenting marginal expression levels. For the first time, we describe time-restricted PKD2-activity influencing early cell fate decision and angiogenesis. During early differentiation (days 0-4), PKD2-activity decreases mesendoderm formation and subsequent cardiovasculogenesis in favour of ectoderm, while promoting sprouting angiogenesis during late differentiation (days 4-14). Consistently, PKD2-loss-of-function analyses demonstrate opposed effects. These findings are confirmed in vivo, as embryoid bodies (EBs), transplanted on CAMs, induce an angiogenic response upon PKD2-overexpression from day 4 of differentiation onwards. Summing up, this thesis presents novel and time-dependent aspects of PKD2- activity during early embryonic development. Our data provide further insight into the complex regulation of angiogenesis, that might even be of clinical interest in the fields of cancer research and regenerative medicine.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (ohne Print-on-Demand)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_opod_v1dc.rights.uri
KeywordPluripotent stem celldc.subject
KeywordEarly lineage specificationdc.subject
KeywordVasculogenesisdc.subject
KeywordAngiogenesisdc.subject
KeywordProtein Kinase D2dc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHNeural stem cellsdc.subject.mesh
MeSHEmbryonic developmentdc.subject.mesh
MeSHCorneal neovascularizationdc.subject.mesh
MeSHProtein kinasesdc.subject.mesh
TitleDirection of angiogenesis by timed activation of protein kinase D2 in murine embryonic stem cellsdc.title
Resource typeDissertationdc.type
Date of acceptance2020-06-25dcterms.dateAccepted
RefereeMüller, Martindc.contributor.referee
RefereeBuckert, Dominikdc.contributor.referee
DOIhttp://dx.doi.org/10.18725/OPARU-33148dc.identifier.doi
PPN173357509Xdc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-33210-7dc.identifier.urn
GNDStammzelledc.subject.gnd
GNDEmbryonalentwicklungdc.subject.gnd
GNDAngiogenesedc.subject.gnd
GNDVaskularisationdc.subject.gnd
GNDProteinkinase Ddc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionUKU. Klinik für Innere Medizin Iuulm.affiliationSpecific
InstitutionUKU. Klinik für Innere Medizin IIuulm.affiliationSpecific
Grantor of degreeMedizinische Fakultätuulm.thesisGrantor
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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