Elaine Dzierzak's lab aims to identify the molecules involved in the generation of haematopoietic stem cells (HSC) and to generate patient-specific HSCs for clinical cell replacement therapies to treat blood-related genetic diseases and leukaemia.
Eoghan Forde - MRC DTP Precision Medicine PhD student
Stem cells are the foundation of somatic tissues and are required for the constant renewal and/or replacement of cells either undergoing normal senescence or damage from exogenous agents. The haematopoietic system requires the constant production of billions of blood cells daily (erythrocytes, lymphocytes, platelets, macrophages, eosinphils, etc). These cells are provided through the functional activity of rare haematopoietic stem cells (HSCs) harbored in the bone marrow of the adult individual. For over 50 years, HSCs have been used in hundreds of thousands of transplantation therapies for blood-related genetic diseases and leukaemias. However, current clinical therapies are limited by the number of HSCs available for such transplantations and attempts to expand such cells ex vivo have been unsuccessful. Well aware of the important clinical uses, HSCs have been the most intensively studied somatic stem cells.
Our lab aims to identify the molecules involved in the generation of HSCs and to generate patient-specific HSCs for clinical cell replacement therapies to treat blood-related genetic diseases and leukaemia.
3D projection of mouse embryonic aorta containing HSC clusters (green). Endothelial cells lining the vasculature are in magenta (Yokomizo T & Dzierzak E, Development. 2010).
Our laboratory was the first to show that HSCs are born in the aorta-gonad-mesonephros region of the developing mammalian embryo. We have recently shown through a live imaging approach that HSCs arise from endothelial cells lining the wall of the embryonic aorta in a natural reprogramming event. This transdifferentiation is known as Endothelial cell-to Hematopoietic cell transition (EHT). We are one of the few groups worldwide that can isolate these special endothelial cells and show that they yield robust transplantable HSCs (the gold-standard for clinically relevant HSCs). Using our unique expertise and novel resources (models and reagents), our laboratory fosters new translational strategies to de novo generate human HSCs from patient somatic cells. Our specific goals are to:
These goals will be realized through novel multi-colour in vivo reporter models and ES/iPS lines indicating EHT in real-time, allowing for the isolation and functional validation of de novo HSC generation. The results will significantly advance haematological research and technology, and should have a major impact on how HSCs are manipulated and used clinically.
Real-time birth of a HSC from an endothelial cell lining the wall of a mouse embryonic aorta (Boisset J-C. et al., Nature. 2010).
Elaine Dzierzak obtained her PhD in Immunology from Yale University and did postdoctoral training in retroviral mediated gene transfer at the Whitehead Institute, MIT. She started her research laboratory at the National Institute for Medical Research, London (UK). In 1996 she moved to the Erasmus University Medical Center in Rotterdam (NL) where she was Professor of Developmental Biology, founder and co-director of the Master of Science Program in Molecular Medicine, and the Founding Director of the Erasmus Stem Cell Institute. She moved to The University of Edinburgh in 2013.