Speaker: Dr Ian McCracken

Presentation title: Transcriptional control of endothelial cell development during human pluripotent stem cell differentiation and coronary vessel formation

Abstract:

Despite improved understanding in recent years, the factors which modulate endothelial cell differentiation and further specification remain largely unknown. My research focuses on combining both human pluripotent stem cell and in vivo based models to unravel the key regulators determining endothelial cell fate in development and regeneration. This work has included mapping the differentiation of hESC to endothelial cells using single cell RNA sequencing (scRNA-seq) to comprehensively profile the transcriptional landscape underpinning this process. Subsequently, we also applied scRNA-seq to characterise the endocardium and coronary endothelium of the human foetal heart, revealing a likely endocardial origin of coronary endothelial cells as well as the discovery of a novel regulator of arteriovenous identity. More recently, I have developed a new in vitro model of coronary endothelial cell specification using endocardial cells derived from human induced pluripotent stem cells. In combination with omics data from in vivo studies, this model offers new opportunities to identify the key regulators of coronary endothelial cell formation thus informing future therapeutic strategies to revascularize the ischaemic adult heart.

Biography:

I completed my PhD training at the University of Edinburgh as part of the MRC Precision Medicine DTP under the supervision of Prof Andrew Baker and Prof Chris Ponting. My PhD research focused on understanding the transcriptional control of endothelial cell development by applying single cell RNA sequencing technologies to human pluripotent stem cell differentiation models. I was also able to characterise the transcriptional landscape of endothelial cells within the developing human heart. Following the completion of my PhD studies, I was awarded an MRC Transition Fellowship to conduct a research project within the lab of Prof Nicola Smart at the University of Oxford. This project aims to elucidate the mechanisms controlling endocardial cell plasticity during development and regeneration using a combination of in vivo and human induced pluripotent stem cell-based methodologies. I have recently been awarded a British Heart Foundation Immediate Research Fellowship which will allow me to continue with this work and explore the development of a gene therapy strategy to promote coronary vessel growth in the ischaemic adult heart.