Alessandro Bertero

Supervisor: Dr Ludovic Vallier

Title: TGF-beta superfamily signalling during human pluripotent stem cells early development

Abstract: Human pluripotent stem cells (hPSC) offer unprecedented opportunities to both study human development and perform cell therapies for diverse diseases including cardiovascular disorders. A bottleneck towards these goals is our still limited understanding of the mechanisms that regulate hPSC differentiation. 

Members of the TGF-beta superfamily such as Activin and BMP4 are key regulators of hPSC early cell-fate decisions as they regulate both self-renewal and mesendoderm differentiation. In particular, Activin and BMP4 activity is spatially regulated during early embryogenesis to finely pattern the primitive streak into many tissue subtypes including hematopoietic mesoderm, pre-cardiac mesoderm, and definitive endoderm.  How this is achieved at a molecular level is still largely unknown.

My project aims to shed light on both the transcriptional and protein-protein interaction networks involving Smad2/3 and Smad1/5/8, the intracellular effectors respectively of Activin and BMP4. Our ultimate goal is to be able to better control hPSC differentiation in order to allow the full exploitation of hPSC to study and cure cardiovascular diseases.

References:

Bertero A, Pauklin S, Mendjan S, Ceder Z, Pedersen R, Vallier L. The role of novel SMAD2/3-binding epigenetic regulators during early cell-fate decisions in human embryonic stem cells (poster selected for oral presentation). International Society of Differentiation Conference 2012 on Stem Cells, Development and Regulation, Amsterdam, The Netherlands.

Bertero A, Pauklin S, Medjan S, Cader Z, Pedersen R, Vallier L. The role of novel SMAD2/3-binding partners during early cell-fate decisions in human embryonic stem cells (poster). Abcam conference: Epigenetic and Stem Cells 2012, Cambridge, UK.