How does developmental history impact haematopoietic molecular convergence? Dissecting the early waves of haemogenic endothelial development

Molecular profiling and lineage tracing studies have revealed that a sub-set of cell types with highly convergent cellular states are commonly generated multiple times during embryonic development by non-identical differentiation pathways. For example, blood forming endothelial cells, called haemogenic endothelium (HE), arise in sequential waves during embryogenesis from various precursor embryonic tissues. How alternative differentiation pathways affect the molecular and functional properties of highly convergent cell types is poorly understood. To explore the role of developmental history in the face of molecular convergence, I will dissect the intrinsic and extrinsic regulatory networks that coordinate HE differentiation.

This project will exploit comprehensive unpublished transcriptomic datasets that capture various waves of HE formation during mouse embryonic development. I have developed a robust embryonic stem cell differentiation model of HE formation that I will use as a platform throughout this project to:
(i) identify extrinsic conditions that drive HE formation via alternative pathways, and
(ii) investigate intrinsic molecular programmes that coordinate HE specification and drive development of its chromatin landscape(s).

This research will improve our understanding of the mechanisms that regulate acquisition of cellular identities during embryogenesis and aid the development of new technologies for regenerative medicine.