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 new alternative source of hematopoietic stem cells. We are interested to learn how HSCs 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 support heart development and participate to repair process and regeneration upon injury.
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.
- European Hematology Association fellowship, €240k, 2016-2019
- Academy of Medical Sciences Springboard award
- Chancellor's Fellowship, University of Edinburgh
- Prof Christer Betsholtz, Immunology, Genetics and Pathology, Uppsala University, Sweden
- Prof Elaine Dzierzak, MRC Centre for Inflamation Research, University of Edinburgh, UK
- Dr Gillian Gray, BHF Centre for Cardiovascular Science, University of Edinburgh, UK
- Prof Kamil R Kranc, MRC Centre for Regenerative Medicine, University of Edinburgh, UK
- Prof Bruno Péault, MRC Centre for Regenerative Medicine, University of Edinburgh, UK
- Harmen van de Werken, Cancer Computational Biology Center, Erasmus Medical Centre, The Netherlands