A systems-level cell-specific view of cardiac cell diversification processes

C. Dondi, K. Pascarel, G. Junion

Most organs are composed of multiple cell types necessary for their function. These cells may have a common origin and undergo a diversification step during development to acquire their own properties. The molecular mechanisms controlling these steps are highly conserved and their understanding is of prime therapeutic utility.

Pluripotent embryonic stem cells have shown their great potential to regenerate tissue. However, one of the current limitations is the formation of complex organs including various cell types.

Our project is to apply innovative genome-wide cell-specific techniques and use Drosophila embryonic cardiac system as a model to uncover genes and molecular mechanisms that lead to a correct cell diversification process and in particular the acquisition of individual cell properties.  

Our objectives:

  • Perform cell-specific transcriptomic analyses in subsets of Drosophila cardioblasts, classify identified candidates, define gene expression signatures and ncRNA that specify different subsets of cardiac cells.
  • Perform cell-specific ribonomic analyses in subsets of Drosophila cardioblast by applying the TRAP method, identify cell specific and stage specific translated mRNA.
  • Perform cell-specific chromatin immunoprecipitation experiments followed by ChIP-seq; identify direct targets of transcription factors, chromatin remodelers and histone post-translational modifications.
  • Analyse expression and functions of identified candidate genes and in particular candidates from the TRAP using GFP-sensors specific to cardiac cell types; build networks of genes and model the process of cardiac diversification.¬†