Cardiovascular disease is the most prevalent cause of death in industrialised countries, and is spreading world-wide. Since in humans the heart cannot regenerate, therapeutic options are limited. Efforts are being made to develop therapeutic cells/ stem cells from various stem cell types, for example from induced pluripotent stem cells. However, what constitutes a suitable therapeutic cell is unclear. The heart develops from two sources of cells, the lateral and the paraxial head mesoderm, also known as 1st and 2nd heart fields. The lateral mesoderm is used-up quickly as it builds the primitive heart. In contrast, the paraxial mesoderm contributes cells for a long period of time and is essential to generate the mature, complex heart. Thus, the paraxial head mesoderm has long-lasting cardiac competence.
This project will characterise the molecular basis of cardiac competence in the paraxial head mesoderm, with the view to develop diagnostic criteria for therapeutic cells. Specifically, we will investigate how heart-specific genes are held in a ready-to-use state, analysing the chromatin configuration of these genes.
As the chicken heart closely resembles the human heart, we will use the chicken embryo as model. A combination of approaches in cell, molecular and developmental biology will be applied, most prominently chromatin immunoprecipitation (ChIP) and Chip-seq analyses.