Sophie McManus

Supervisor:   Sanjay Sinha  co-supervised by Helle Jørgensen

Title:  Origins and development of coronary smooth muscle cells

Abstract:

Vascular diseases such as atherosclerosis are associated with vascular smooth muscle cell (VSMC) reactivation of embryonic programmes. Hence understanding origins and development of VSMC is likely to yield disease insight.Coronary (C)VSMC originate from the epicardium, a heterogeneous cell layer essential to cardiovascular development; two main epicardial subpopulations have been identified. However it is unknown which subpopulations form CVSMC. VSMC investment in coronary arteries is also poorly understood. We hypothesise that distinct epicardial subpopulations have different CVSMC-forming propensities and that origin-specific VSMC display functional differences. Secondly, we hypothesise that clonal CVSMC proliferation forms the mature coronary vasculature. Hence we aim (i) to define development of different epicardial subpopulations in human tissue using embryonic stem cell reporter lines; (ii) to define which epicardial subpopulations form CVSMC, and (iii) characterise developmental CVSMC proliferation in vivo using the Myh11-CreERt2 ‘Confetti’ system. Understanding CVSMC development is critically important for work on coronary disease and regenerative strategies.