TS033 Integrative studies on the role of Ccbe1 in cardiogenesis: from the embryo to ES cell derived cardiac tissue

A central challenge for the future perspective of cardiac regenerative medicine is the generation of large numbers of patient-specific cardiac myocytes. Ccbe1 encodes a secreted molecule that was firstly identified using an Affymetrix GeneChip differential screen for chick heart precursor cells expressed genes (Bento et al., 2011). In mouse and chick, Ccbe1 is expressed in major cardiac progenitor lineages that contribute to distinct heart structures during heart organogenesis (Facucho-Oliveira et al., 2011). Moreover, analysis of gain and loss of function performed in both mouse and chick embryos showed abnormal cardiac morphogenesis and aberrant chamber formation further elucidating the role of Ccbe1 for cardiac development. Similarly, in mouse and human ES cells, increased levels of Ccbe1 expression were detected after cardiac lineage commitment demonstrating well-coordinated expression of various early and late cardiac specific markers and Ccbe1. Knock-Down in mouse and human ES cells demonstrated the requirement of Ccbe1 for proper cardiogenesis. Modulation of mCcbe1 activity in differentiating mES cells using media supplemented with mCcbe1 recombinant protein has demonstrated a remarkable inductive potential of mCcbe1 to enhance cardiogenesis. Taken together, this data strongly suggest that Ccbe1 has the ability to direct the expression of cardiac inducers and to control cardiac progenitor expansion in vitro and in vivo, allowing the generation of non-genetically manipulated cardiac cells from a renewable cell source for regenerative cardiovascular medicine.