Málstofa Lífvísindaseturs - Dr. Guðrún Valdimarsdóttir

Málstofa Lífvísindaseturs HÍ fimmtudaginn 26. april kl. 12:00 í stofu 343 Læknagarði

Fyrirlesari: Dr. Guðrún Valdimarsdóttir, dósent við Læknadeild Háskóla Íslands

Titill: EGFL7 mediates BMP9-induced sprouting angiogenesis of endothelial cells derived from human embryonic stem cells

Ágrip: Human embryonic stem cells (hESCs) are instrumental to characterize molecular mechanisms of human vascular development and disease. Bone Morphogenetic Proteins (BMPs) play a pivotal role in cardiovascular development in mice but their importance for vascular cells derived from hESC has not yet been fully explored.

Here, we demonstrate that BMP9 promotes, via its receptor ALK1 and SMAD1/5 activation, sprouting angiogenesis of hESC-derived endothelial cells (ECs). Epidermal Growth Factor-Like domain 7 (EGFL7) is a secreted angiogenic factor that is expressed by and acts on ECs. Expression of EGFL7 is highest in proliferating vasculature and regulates tubulogenesis in zebrafish and vascular patterning in mice (Nichol et al., 2012). We show that EGFL7 is a downstream target of BMP9-SMAD1/5 mediated signalling, and that EGFL7 promotes expansion of endothelium via interference with  NOTCH signalling, activation of ERK, and remodelling of the extracellular matrix. CRISPR/Cas9-mediated deletion of EGFL7 highlights the critical role of EGFL7 in the BMP9-induced endothelial sprouting and the promotion of the angiogenesis.