Deep sequencing analysis of MesP1 dependent cardiovascular signalling pathways during stem cell differentiation

• Applicant: Professor Dr. Robert David
• Subject Area: Cardiology, Angiology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 197123046

The proliferative potential of stem cell derived cardiomyocytes is limited and reasonable yields to repair a human infarcted heart have yet to be achieved. It is crucial to decipher the biological processes underlying cardiovascular stem cell differentiation in order to preprogram pluripotent cells for cardiovascular cell therapy and tissue engineering. We have shown that the transcription factor MesP1 represents a master regulator sufficient to induce cardiovasculogenesis in stem cells as well as vertebrate embryos. Thereby, we defined the Dkk-1 promoter as a direct target of MesP1 leading to blockage of canonical wnt-signaling. More recently we demonstrated proof of principle for cardiovascular subtype specific programming of ES cells: MesP1 forced the appearance of early/intermediate type cardiomyocytes whereas Nkx2.5 led to preferentially differentiated ventricular cells. Relying on stably and inducible MesP1 overexpressing ES cell lines here we plan the analysis of cardiovascular stem cell differentiation using a global approach based on deep sequencing at the mRNA (Transcriptome) level. Thereby MesP1 positive will be compared to MesP1 negative lateral plate mesodermal cells. In addition novel MesP1 target promoters will be identified via ChIP-Seq. Overall we expect to obtain novel important information of yet unknown signalling pathways and factors driving these events as well as to come up with novel surface markers possibly allowing purification of cardiovascular precursor cells without genetic modification.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Wolfgang-M. Franz