Giovanni Canu

Supervisor: Prof Ludovic Vallier

Co-supervisor: Prof Roger Patient

Title: Cell-cycle dependent mechanisms controlling differentiation of haematopoietic stem cells

Abstract: Haematopoietic stem cells (HSCs) in the bone marrow need to exert an accurate balance between quiescence, proliferation and differentiation in order to maintain blood homeostasis. Our group has recently shown that cell-cycle directs cell fate decisions in human pluripotent stem cells (hPSCs) through regulators of the cell-cycle such as Cyclin D-CDK4/6 complexes which control signalling pathways directing cell fate choice. Absence of Cyclin Ds, CDKs or other regulators of the cell-cycle have been shown to be associated with haematopoietic defects in vivo, suggesting that similar mechanisms could be important during blood cells production.

The aim of this project is to define the role of cell-cycle dependent mechanisms in haematopoiesis. We will use hPSCs as an in vitro model to study early development and differentiation of haematopoietic progenitors. This approach will enable us to study the molecular pathways that connect the cell-cycle to the generation of blood lineages. Importantly, key findings obtained in vitro will be validated in vivo using zebrafish, an animal model commonly used in haematopoiesis. Ultimately, the resulting knowledge will be used to develop new protocols for the production of haematopoietic cells from hPSCs, based on simple manipulation of the cell-cycle.