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Functional genomics of ORP2 or protrudin knockdown in human umbilical vein endothelial cells

Show simple item record 2019-10-30T10:38:01Z 2019-10-30T10:38:01Z 2019-10-30
dc.title Functional genomics of ORP2 or protrudin knockdown in human umbilical vein endothelial cells en
ethesis.discipline.URI none
ethesis.faculty Bio- ja ympäristötieteellinen tiedekunta fi
ethesis.faculty Faculty of Biological and Environmental Sciences en
ethesis.faculty Bio- och miljövetenskapliga fakulteten sv
ethesis.faculty.URI Helsingin yliopisto fi University of Helsinki en Helsingfors universitet sv
dct.creator Taskinen, Juuso
dct.issued 2019
dct.language.ISO639-2 eng
dct.abstract Human umbilical vein endothelial cells are responsible for maintaining and forming new vessels from existing ones, in a biological process called sprouting angiogenesis. Sprouting angiogenesis is a crucial mechanism for the resolution of hypoxia and normal development of tissues. It also plays a key role in internal plague hemorrhages, which can lead to embolisms and other cardiovascular complications. Angiogenesis is also crucial for cancer development. Sprouting angiogenesis is initiated by hypoxic tissue excreted vascular endothelial growth factor gradient, which induces normal endothelial cells into either a proliferative stalk cell or a signal sensing tip cell phenotype. Both of these cell types depend on the rapid flow of lipids to their plasma membrane, either to form plasma membrane protrusions in tip cells or as new plasma membrane material in dividing stalk cells. This flow is envisioned to involve both vesicle-mediated and non-vesicular mechanisms. A major non-vesicular route of lipid transfer occurs at membrane contact sites via lipid transport proteins. Furthermore, lipids can be transported to the plasma membrane by the direct fusion of vesicles or endosomes with the plasma membrane This thesis set out to explore the role of two membrane contact site proteins, oxysterol-binding protein- related protein 2 and protrudin, in angiogenesis and lipid transfer. Their role was examined by RNA-sequencing transient knock-down samples of these proteins in HUVECs. The RNA-sequencing data was examined by differential expression, gene ontology overrepresentation and gene set enrichment analyses. Gene expression analysis provided almost 10 000 significantly changed transcripts (adjusted p-values < 0.05), in each silenced cell type. The distribution of differentially expressed genes in oxysterol-binding protein- related protein 2 silenced cells, is skewed toward negative fold changes, whereas the distribution of differentially expressed genes in protrudin silenced samples is normally distributed. The results also show significant changes in gene ontologies related to proliferation, cell cycle, angiogenesis as well as hypoxia in both sample types. Gene set enrichment analysis showed upregulation in angiogenesis related pathways, such as the PI3K-Akt and MAPK pathways, in both samples. Significant downregulation was present in cell cycle related pathways and cholesterol biosynthesis pathway in both ORP2 and protrudin silenced samples. en
dct.subject angiogeneesi fi
dct.subject endoteelisolu fi
dct.subject geenien ilmentyminen fi
dct.subject ORP2 fi
dct.subject protrudiini fi
dct.subject RNA-sekvensointi fi
dct.subject kalvokontaktiproteiini fi
dct.subject funktionaalinen genetiikka fi
dct.subject RNA-sequencing en
dct.subject ORP2 en
dct.subject protrudin en
dct.subject membrane contacts site en
dct.subject angiogenesis en
dct.subject endothelial cell en
dct.subject gene expression en
dct.subject functional genomics en
dct.language en
ethesis.language englanti fi
ethesis.language English en
ethesis.language engelska sv
ethesis.supervisor Olkkonen, Vesa
ethesis.supervisor Arora, Amita
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
ethesis.thesistype pro gradu-avhandlingar sv
dct.identifier.ethesis E-thesisID:3216f972-9143-4811-b9bb-a05f947209ea
ethesis-internal.timestamp.reviewStep 2019-08-15 08:25:18:618
ethesis.principalprofessor Siljander, Pia
dct.identifier.urn URN:NBN:fi:hulib-201910303803
dc.type.dcmitype Text
dct.alternative ORP2 ja protrudiini hiljennyksen funktionaalinen genetiikka, ihmisen napanuoran suonen soluissa fi
ethesis.facultystudyline Molekulaaristen ja analyyttisten biotieteiden opintosuunta fi
ethesis.facultystudyline Molecular and Analytical Health Biosciences en
ethesis.facultystudyline Molekylärä och analytiska biovetenskaper sv
ethesis.mastersdegreeprogram Genetiikan ja molekulaaristen biotieteiden maisteriohjelma fi
ethesis.mastersdegreeprogram Master's Programme in Genetics and Molecular Biosciences en
ethesis.mastersdegreeprogram Magisterprogrammet i genetik och molekylära biovetenskaper sv

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