Líffræðifélag Íslands
Líffræðiráðstefnan 2015
Erindi/veggspjald / Talk/poster E29
Anne Richter (1), Ellen Dagmar Björnsdottir (1), Tobias Roland Richter (1), Gudrun Valdimarsdottir (1)
(1) Dept. of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland.
Kynnir / Presenter: Anne Richter
Tengiliður / Corresponding author: Anne Richter (anner@hi.is)
Understanding key elements in cellular and molecular pathways in human embryonic stem cell (hESC) vascular commitment is instrumental in defining novel therapeutic targets and cell replacement therapies. Our knowledge on the molecular mechanisms that regulate cardiovascular development in human is relatively limited. A pivotal role of TGFβ family members as well as the Epidermal Growth Factor-Like domain 7 (EGFL7) and microRNA-126 (mir-126) has been shown in mice cardiovascular development, but their underlying molecular mechanisms are still unclear. Here, we study the signal transduction pathways during hESC vascular development and hESC derived endothelial sprouting. hESC were differentiated towards the vascular lineage using very efficient monolayer cultures for expression analysis but inducing embryoid bodies (EB) to assess EB sprouting. Afterwards, mesodermal cells/EB were stimulated with different members/inhibitors of the TGFβ superfamily. We show that BMP9/ALK1 promotes vascular commitment of hESC and sprouting via Smad1/5 activation and Id1 upregulation. Importantly, we demonstrate in CRISPR knock-out experiments that EGFL7 affects NOTCH and VEGFR-2 signalling pathways in order to activate cell proliferation, differentiation and angiogenesis. Our study illustrates the complex role of the TGFβ superfamily during hESC vascular development and endothelial sprouting.