DRIVING ENDOTHELIAL CELL SPECIFICATION IN PLURIPOTENT STEM CELLS AND IDENTIFYING ORGAN(OID) SPECIFIC VASCULARIZATION FOR REGENERATIVE MEDICINE

The vascular endothelium is essential to maintain vascular tone in health; but is central to aberrant function of both large and small blood vessels in vascular disease. Within each organ, the endothelium is highly heterogenous. Studying vascularization principles and mechanisms of organs and organoids and developing new organ(oid)-specific strategies is important for understanding organ(oid)-specific functions of the vasculature and defining new strategies for regenerative medicine.
Proposed Aims: (1) To develop cell culture and in vivo modalities to support the maintenance of pluripotent-derived cells as organoids driving endothelial cell maturation, (2) To assess this maturation and specification status of vascular endothelial at the transcriptional level using single cell RNAseq, (3) To probe transcription factor networks underpinning maturation and specification using advanced informatics, ATAC-seq and CRISPRi/a approaches in stem cell organoid models. This project brings together the expertise of both labs (pluripotent cells, endothelial cell function and heterogeneity, functional metabolic analysis of derived populations and essential paracrine interactions between cell types) of both labs and benefits from additional collaboration with Ton Rabelink (The Netherlands). The candidate will be based on Edinburgh but be expected to spend extended periods of time for research in Leuven.