Centre for Regenerative Medicine

Mihaela Crisan Research Group

Blood vessel stem cell biology

Hematopoietic stem cells (HSCs) generate all blood cells throughout the entire lifespan. HSC transplantation can cure many children and adults affected by leukaemia. Donors are limited and thus there is a requirement for a new alternative source of hematopoietic stem cells. We are interested to learn how HSCs are naturally born during development. To do this, we study the surrounding vascular microenvironment in which the first adult-type hematopoietic stem cells appear (dorsal aorta) and expand (foetal liver). In parallel, we want to understand whether pericytes (cells which are found in the walls of the body's smallest blood vessels) support heart development and participate to repair process and regeneration upon injury.

Dr Mihaela Crisan

Group Leader and Chacellor's Fellow

Contact details

Microscope images of mouse embryonic dorsal aorta at the time of hematopoietic stem cell emergence
Three-dimensional confocal imaging of the mouse embryonic dorsal aorta at the time of the hematopoietic stem cell emergence (E10.5). Left: hematopoietic cells form clusters in the dorsal aorta (cyan). Right: the dorsal aorta is surrounded by endothelial cells (purple) and vascular smooth muscle cells (green/yellow) involved in the hematopoietic support.

Aims and areas of interest

To date, hematopoietic stem cells (HSCs) cannot be generated and expanded ex vivo. In vivo, HSCs generate from hemogenic endothelial cells from the dorsal embryonic aorta and this requires intrinsic and extrinsic factors from the surrounding microenvironment. The cellular composition of the microenvironment is unknown. It comprises endothelial cells and mesenchymal cells. Our hypothesis is that pericytes and other perivascular mesenchymal cells have distinct roles in hematopoietic development and that a subset of pericytes is required to generate HSCs. They may have an intrinsic genetic programme or establish a particular cell contact with endothelial cells which dictate, in time and space, the birth of HSCs. To address this question, we genetically manipulate pericytes and other perivascular cells in the immediate vicinity of hemogenic endothelial cells to disrupt HSC generation in vivo. Using similar strategies, we test whether pericytes play a role in the heart repair process and regeneration upon injury at adult stage. Finally, we aim to understand what is/are the origin(s) of pericytes during mouse development. We use in the lab state-of-the-art technologies such as confocal imaging, live imaging, transgenic mice, cre-lox system as well as transcriptome and metabolome in close collaboration with other groups. Our work has implications in both leukemia and myocardium infarct.

Group members

David Craig, BHF PhD student

Madalena Marques, Research Assistant

Funders

AFM (Association Francaise pour la Myopathie)

European Hematology Association fellowship

Academy of Medical Sciences Springboard award

Chancellor's Fellowship, University of Edinburgh

Collaborators

Prof Christer Betsholtz, Immunology, Genetics and Pathology, Uppsala University, Sweden

Prof Elaine Dzierzak, Centre for Inflamation Research, University of Edinburgh, UK

Dr Gillian Gray, BHF Centre for Cardiovascular Science, University of Edinburgh, UK

Prof Bruno Péault, Centre for Regenerative Medicine, Centre for Cardiovascular Science, University of Edinburgh, UK

Dr Adriana Tavares, Centre for Cardiovascular Science, University of Edinburgh, UK

Professor Clare Isacke, Institute of Cancer Research, London